Chapter 8 : Innate Immune Response and Inflammation: Roles in Pathogenesis and Protection ()

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Innate Immune Response and Inflammation: Roles in Pathogenesis and Protection (), Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817336/9781555816773_Chap08-1.gif /docserver/preview/fulltext/10.1128/9781555817336/9781555816773_Chap08-2.gif


Although spotted fever group rickettsiae (SFGR) and typhus group rickettsiae (TGR) represent two major antigenically defined and historically well-known subdivisions of pathogenic species, recent in-depth characterization by neighbor-joining phylodendrogramic analysis has distributed rickettsiae into ancestral, spotted fever, typhus, and transitional subgroups. Importantly, well-established and widely accepted in vivo models of infection closely mimicking the pathogenesis of Rocky Mountain spotted fever (RMSF) and epidemic typhus in humans employ infection of susceptible mouse strains with and , respectively. The endothelial cell responses to and signaling mechanisms that determine the interplay between the host and the unique rickettsial pathogen, which is capable of escaping immune surveillance to cause recrudescent infections, remain critically important but neglected areas of scientific inquiry. Thus, one of the major critical gaps in the understanding of rickettsial pathogenesis is the definition of the biological basis of rickettsial affinity and consequent interactions with vascular endothelium. infection induces a biphasic pattern of NF-ΚB activation in cultured human endothelial cells that is characterized by an early transient activation phase and a late sustained phase. There is increasing recognition that apoptosis, a tightly regulated process of altruistic suicide, plays a central role in complex interactions between an invading pathogen and host cell defense. First recognized for their ability to impede viral replication, interferons (IFNs) play a critical role in determining host survival in response to viral infection. During bacterial infections, IFN signaling defends the host by integrating early innate immune responses with later events.

Citation: Sahni S, Rydkina E, Simpson-Haidaris P. 2012. Innate Immune Response and Inflammation: Roles in Pathogenesis and Protection (), p 243-269. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch8
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Endothelial cell functions under normal physiological conditions and inresponse to activation. PDGF, platelet-derived growth factor. doi:10.1128/9781555817336.ch8.f1

Citation: Sahni S, Rydkina E, Simpson-Haidaris P. 2012. Innate Immune Response and Inflammation: Roles in Pathogenesis and Protection (), p 243-269. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch8
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Summary of the current state of knowledge and potential future directions for investigations focused on interactions between pathogenic species and their preferred host niche, the vascular endothelium. doi:10.1128/9781555817336.ch8.f2

Citation: Sahni S, Rydkina E, Simpson-Haidaris P. 2012. Innate Immune Response and Inflammation: Roles in Pathogenesis and Protection (), p 243-269. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch8
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Ameriso, S. F.,, A. R. Villamil,, C. Zedda,, J. C. Parodi,, S. Garrido,, M. I. Sarchi,, M. Schultz,, J. Boczkowski,, and G. E. Sevlever. 2005. Heme oxygenase-1 is expressed in carotid atherosclerotic plaques infected by Helicobacter pylori and is more prevalent in asymptomatic subjects. Stroke 36: 1896 1900.PubMed CrossRef
2. Andersson, S. G.,, A. Zomorodipour,, J. O. Andersson,, T. Sicheritz-Pontén,, U. C. Alsmark,, R. M. Podowski,, A. K. Näslund,, A. S. Eriksson,, H. H. Winkler,, and C. G. Kurland. 1998. The genome sequence of Rickettsia prowazekii and the origin of mitochondria. Nature 396: 133 140.PubMed CrossRef
3. Apperson, C. S.,, B. Engber,, W. L. Nicholson,, D. G. Mead,, J. Engel,, M. J. Yabsley,, K. Dail,, J. Johnson,, and D. W. Watson. 2008. Tick-borne diseases in North Carolina: is “ Rickettsia amblyommii” a possible cause of rickettsiosis reported as Rocky Mountain spotted fever? Vector Borne Zoonotic Dis. 8: 597 606.PubMed CrossRef
4. Azri, S.,, and K. W. Renton. 1991. Factors involved in the depression of hepatic mixed function oxidase during infections with Listeria monocytogenes. Int. J. Immunopharmacol. 13: 197 204.PubMed
5. Baetz, A.,, S. Zimmermann,, and A. H. Dalpke. 2007. Microbial immune evasion employing suppressor of cytokine signaling (SOCS) proteins. Inflamm. Allergy Drug Targets 6: 160 167.PubMed
6. Balistreri, C. R.,, G. Candore,, D. Lio,, G. Colonna-Romano,, G. Di Lorenzo,, P. Mansueto,, G. Rini,, S. Mansueto,, E. Cillari,, C. Franceschi,, and C. Caruso. 2005. Role of TLR4 receptor polymorphisms in Boutonneuse fever. Int. J. Immunopathol. Pharmacol. 18: 655 660.PubMed
7. Balraj, P.,, C. Nappez,, D. Raoult,, and P. Renesto. 2008. Western-blot detection of RickA within spotted fever group rickettsiae using a specific monoclonal antibody. FEMS Microbiol. Lett. 286: 257 262.PubMed CrossRef
8. Barañano, D. E.,, M. Rao,, C. D. Ferris,, and S. H. Snyder. 2002. Biliverdin reductase: a major physiologic cytoprotectant. Proc. Natl. Acad. Sci. USA 99: 16093 16098.PubMed CrossRef
9. Bechah, Y.,, C. Capo,, G. Grau,, D. Raoult,, and J. L. Mege. 2009. Rickettsia prowazekii infection of endothelial cells increases leukocyte adhesion through αvβ3 integrin engagement. Clin. Microbiol. Infect. 15( Suppl. 2): 249 250.PubMed CrossRef
10. Bechah, Y.,, C. Capo,, J. L. Mege,, and D. Raoult. 2008a. Rickettsial diseases: from Rickettsia-arthropod relationships to pathophysiology and animal models. Future Microbiol. 3: 223 236.PubMed CrossRef
11. Bechah, Y.,, C. Capo,, D. Raoult,, and J. L. Mege. 2008b. Infection of endothelial cells with virulent Rickettsia prowazekii increases the transmigration of leukocytes. J. Infect. Dis. 197: 142 147.PubMed CrossRef
12. Bechelli, J. R.,, E. Rydkina,, P. M. Colonne,, and S. K. Sahni. 2009. Rickettsia rickettsii infection protects human microvascular endothelial cells against staurosporine-induced apoptosis by a cIAP 2-independent mechanism. J. Infect. Dis. 199: 1389 1398.PubMed CrossRef
13. Billings, A. N.,, H. M. Feng,, J. P. Olano,, and D. H. Walker. 2001. Rickettsial infection in murine models activates an early anti-rickettsial effect mediated by NK cells and associated with production of gamma interferon. Am. J. Trop. Med. Hyg. 65: 52 56.PubMed
14. Bogatcheva, N. V.,, S. M. Dudek,, J. G. Garcia,, and A. D. Verin. 2003. Mitogen-activated protein kinases in endothelial pathophysiology. J. Investig. Med. 51: 341 352.PubMed
15. Brouard, S.,, L. E. Otterbein,, J. Anrather,, E. Tobiasch,, F. H. Bach,, A. M. K. Choi,, and M. P. Soares. 2000. Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis. J. Exp. Med. 192: 1015 1025.PubMed CrossRef
16. Bussolati, B.,, A. Ahmed,, H. Pemberton,, R. C. Landis,, F. Di Carlo,, D. O. Haskard,, and J. C. Mason. 2004. Bifunctional role for VEGF-induced heme oxygenase-1 in vivo: induction of angiogenesis and inhibition of leukocytic infiltration. Blood 103: 761 766.PubMed CrossRef
17. Carneiro, L. A.,, J. G. Magalhaes,, I. Tattoli,, D. J. Philpott,, and L. H. Travassos. 2008. Nod-like proteins in inflammation and disease. J. Pathol. 214: 136 148.PubMed CrossRef
18. Chen, Z.,, J. Hagler,, V. J. Palombella,, F. Melandri,, D. Scherer,, D. Ballard,, and T. Maniatis. 1995. Signal-induced site-specific phosphorylation targets IκBα to the ubiquitin-proteasome pathway. Genes Dev. 9: 1586 1597.PubMed CrossRef
19. Choi, K. S.,, D. G. Scorpio,, and J. S. Dumler. 2004. Anaplasma phagocytophilum ligation to Toll-like receptor (TLR) 2, but not to TLR4, activates macrophages for nuclear factor-κB nuclear translocation. J. Infect. Dis. 189: 1921 1925.PubMed CrossRef
20. Cillari, E.,, S. Milano,, P. D’Agostino,, F. Arcoleo,, G. Stassi,, A. Galluzzo,, P. Richiusa,, C. Giordano,, P. Quartararo,, P. Colletti,, G. Gambino,, C. Mocciaro,, A. Spinelli,, G. Vitale,, and S. Mansueto. 1996. Depression of CD4 T cell subsets and alteration in cytokine profile in boutonneuse fever. J. Infect. Dis. 174: 1051 1057.PubMed CrossRef
21. Clifton, D. R.,, R. A. Goss,, S. K. Sahni,, D. van Antwerp,, R. B. Baggs,, V. J. Marder,, D. J. Silverman,, and L. A. Sporn. 1998. NF-κB-dependent inhibition of apoptosis is essential for host cell survival during Rickettsia rickettsii infection. Proc. Natl. Acad. Sci. USA 95: 4646 4651.PubMed
22. Clifton, D. R.,, E. Rydkina,, R. S. Freeman,, and S. K. Sahni. 2005a. NF-κB activation during Rickettsia rickettsii infection of endothelial cells involves the activation of catalytic IκB kinases IKKα and IKKβ and phosphorylation-proteolysis of the inhibitor protein IκBα. Infect. Immun. 73: 155 165.PubMed CrossRef
23. Clifton, D. R.,, E. Rydkina,, H. Huyck,, G. Pryhuber,, R. S. Freeman,, D. J. Silverman,, and S. K. Sahni. 2005b. Expression and secretion of chemotactic cytokines IL-8 and MCP-1 by human endothelial cells after Rickettsia rickettsii infection: regulation by nuclear transcription factor NF-κB. Int. J. Med. Microbiol. 295: 267 278.PubMed
24. Damas, J. K.,, M. Jensenius,, T. Ueland,, K. Otterdal,, A. Yndestad,, S. S. Froland,, J. M. Rolain,, B. Myrvang,, D. Raoult,, and P. Aukrust. 2006. Increased levels of soluble CD40L in African tick bite fever: possible involvement of TLRs in the pathogenic interaction between Rickettsia africae, endothelial cells, and platelets. J. Immunol. 177: 2699 2706.PubMed
25. Dantas-Torres, F. 2007. Rocky Mountain spotted fever. Lancet Infect. Dis. 7: 724 732.PubMed CrossRef
26. Davidge, S. T. 2001. Prostaglandin H synthase and vascular function. Circ. Res. 89: 650 660.PubMed CrossRef
27. De las Heras, D.,, J. Fernández,, P. Ginès,, A. Cárdenas,, R. Ortega,, M. Navasa,, J. A. Barberá,, B. Calahorra,, M. Guevara,, R. Bataller,, W. Jiménez,, V. Arroyo,, and J. Rodés. 2003. Increased carbon monoxide production in patients with cirrhosis with and without spontaneous bacterial peritonitis. Hepatology 38: 452 459.PubMed CrossRef
28. Demma, L. J.,, M. Traeger,, D. Blau,, R. Gordon,, B. Johnson,, J. Dickson,, R. Ethelbah,, S. Piontkowski,, C. Levy,, W. L. Nicholson,, C. Duncan,, K. Heath,, J. Cheek,, D. L. Swerdlow,, and J. H. McQuiston. 2006. Serologic evidence for exposure to Rickettsia rickettsii in eastern Arizona and recent emergence of Rocky Mountain spotted fever in this region. Vector Borne Zoonotic Dis. 6: 423 429. ( Erratum, 7:106, 2007.).PubMed CrossRef
29. Demma, L. J.,, M. S. Traeger,, W. L. Nicholson,, C. D. Paddock,, D. M. Blau,, M. E. Eremeeva,, G. A. Dasch,, M. L. Levin,, J. Singleton, Jr.,, S. R. Zaki,, J. E. Cheek,, D. L. Swerdlow,, and J. H. McQuiston. 2005. Rocky Mountain spotted fever from an unexpected tick vector in Arizona. N. Engl. J. Med. 353: 587 594.PubMed CrossRef
30. Denk, A.,, M. Goebeler,, S. Schmid,, I. Berberich,, O. Ritz,, D. Lindemann,, S. Ludwig,, and T. Wirth. 2001. Activation of NF-κB via the IκB kinase complex is both essential and sufficient for proinflammatory gene expression in primary endothelial cells. J. Biol. Chem. 276: 28451 28458.PubMed CrossRef
31. de Sousa, R.,, A. França,, S. D. Nobrega,, A. Belo,, M. Amaro,, T. Abreu,, J. Poças,, P. Proença,, J. Vaz,, J. Torgal,, F. Bacellar,, N. Ismail,, and D. H. Walker. 2008. Host- and microbe-related risk factors for and pathophysiology of fatal Rickettsia conorii infection in Portuguese patients. J. Infect. Dis. 198: 576 585.PubMed CrossRef
32. de Sousa, R.,, N. Ismail,, S. D. Nobrega,, A. França,, M. Amaro,, M. Anes,, J. Poças,, R. Coelho,, J. Torgal,, F. Bacellar,, and D. H. Walker. 2007. Intralesional expression of mRNA of interferon-γ, tumor necrosis factor-α, interleukin-10, nitric oxide synthase, indoleamine-2,3-dioxygenase, and RANTES is a major immune effector in Mediterranean spotted fever rickettsiosis. J. Infect. Dis. 196: 770 781.PubMed CrossRef
33. DiDonato, J. A.,, M. Hayakawa,, D. M. Rothwarf,, E. Zandi,, and M. Karin. 1997. A cytokine-responsive IκB kinase that activates the transcription factor NF-κB. Nature 388: 548 554.PubMed CrossRef
34. Dignat-George, F.,, N. Teysseire,, M. Mutin,, N. Bardin,, G. Lesaule,, D. Raoult,, and J. Sampol. 1997. Rickettsia conorii infection enhances vascular cell adhesion molecule-1- and intercellular adhesion molecule-1-dependent mononuclear cell adherence to endothelial cells. J. Infect. Dis. 175: 1142 1152.PubMed CrossRef
35. Drancourt, M.,, M.-C. Allessi,, P.-Y. Levy,, I. Juhan-Vague,, and D. Raoult. 1990a. Secretion of tissue-type plasminogen activator and plasminogen activator inhibitor by Rickettsia conroii and Rickettsia rickettsii-infected cultured endothelial cells. Infect. Immun. 58: 2459 2463.PubMed
36. Drancourt, M.,, D. Raoult,, J. R. Harle,, H. Chaudet,, F. Janbon,, C. Charrel,, and H. Gallais. 1990b. Biological variations in 412 patients with Mediterranean spotted fever. Ann. N. Y. Acad. Sci. 590: 39 50.PubMed CrossRef
37. Driskell, L. O.,, X.-J. Yu,, L. Zhang,, Y. Liu,, V. L. Popov,, D. H. Walker,, A. M. Tucker,, and D. O. Wood. 2009. Directed mutagenesis of the Rickettsia prowazekii pld gene encoding phospholipase D. Infect. Immun. 77: 3244 3248.PubMed CrossRef
38. Dumler, J. S.,, and D. H. Walker. 2005. Rocky Mountain spotted fever—changing ecology and persisting virulence. N. Engl. J. Med. 353: 551 553.PubMed CrossRef
39. Dyer, L. A.,, and C. Patterson. 2010. Development of the endothelium: an emphasis on heterogeneity. Semin. Thromb. Hemost. 36: 227 235.PubMed CrossRef
40. Eremeeva, M. E.,, G. A. Dasch,, and D. J. Silverman,. 2000. Interaction of rickettsiae with eukaryotic cells. Adhesion, entry, intracellular growth, and host cell responses, p. 479 516. In T. A. Oelschlaeger, and J. Hacker (ed.), Bacterial Invasion into Eukaryotic Cells. Kluwer Academic/Plenum Publishers, New York, NY.
41. Eremeeva, M. E.,, G. A. Dasch,, and D. J. Silverman. 2001. Quantitative analyses of variations in the injury of endothelial cells elicited by 11 isolates of Rickettsia rickettsii. Clin. Diagn. Lab. Immunol. 8: 788 796.PubMed CrossRef
42. Eremeeva, M. E.,, L. A. Santucci,, V. L. Popov,, D. H. Walker,, and D. J. Silverman,. 1999. Rickettsia rickettsii infection of human endothelial cells: oxidative injury and reorganization of the cytoskeleton, p. 128 144. In D. Raoult, and P. Brouqui (ed.), Rickettsiae and Rickettsial Diseases at the Turn of the Third Millennium. Elsevier Press, Paris, France.
43. Eremeeva, M. E.,, and D. J. Silverman. 1998. Rickettsia rickettsii infection of the EA.hy 926 endothelial cell line: morphological response to infection and evidence for oxidative injury. Microbiology 144: 2037 2048.PubMed CrossRef
44. Esposti, M. D. 2002. The roles of Bid. Apoptosis 7: 433 440.PubMed CrossRef
45. Fan, H.,, and J. A. Cook. 2004. Molecular mechanisms of endotoxin tolerance. J. Endotoxin Res. 10: 71 84.PubMed CrossRef
46. Fang, M.,, H. Dai,, G. Yu,, and F. Gong. 2005. Gene delivery of SOCS3 protects mice from lethal endotoxic shock. Cell. Mol. Immunol. 2: 373 377.PubMed
47. Fang, R.,, N. Ismail,, L. Soong,, V. L. Popov,, T. Whitworth,, D. H. Bouyer,, and D. H. Walker. 2007. Differential interaction of dendritic cells with Rickettsia conorii: impact on host susceptibility to murine spotted fever rickettsiosis. Infect. Immun. 75: 3112 3123.PubMed CrossRef
48. Feng, H. M.,, V. L. Popov,, and D. H. Walker. 1994. Depletion of gamma interferon and tumor necrosis factor alpha in mice with Rickettsia conorii-infected endothelium: impairment of rickettsicidal nitric oxide production resulting in fatal, overwhelming rickettsial disease. Infect. Immun. 62: 1952 1960.PubMed
49. Feng, H. M.,, and D. H. Walker. 2000. Mechanisms of intracellular killing of Rickettsia conorii in infected human endothelial cells, hepatocytes, and macrophages. Infect. Immun. 68: 6729 6736.PubMed CrossRef
50. Feng, H. M.,, T. Whitworth,, V. Popov,, and D. H. Walker. 2004. Effect of antibody on the rickettsia-host cell interaction. Infect. Immun. 72: 3524 3530.PubMed CrossRef
51. Galley, H. F.,, and N. R. Webster. 2004. Physiology of the endothelium. Br. J. Anaesth. 93: 105 113.
52. Gillespie, J. J.,, K. Williams,, M. Shukla,, E. E. Snyder,, E. K. Nordberg,, S. M. Ceraul,, C. Dharmanolla,, D. Rainey,, J. Soneja,, J. M. Shallom,, N. D. Vishnubhat,, R. Wattam,, A. Purkayastha,, M. Czar,, O. Crasta,, J. C. Setubal,, A. F. Azad,, and B. S. Sobral. 2008. Rickettsia phylogenomics: unwinding the intricacies of obligate intracellular life. PLoS One 3: e2018.PubMed CrossRef
53. Gonder, J. C.,, R. H. Kenyon,, and C. E. Pedersen, Jr. 1980. Epidemic typhus infection in cynomolgus monkeys ( Macaca fascicularis). Infect. Immun. 30: 219 223.PubMed
54. Gouin, E.,, C. Egile,, P. Dehoux,, V. Villiers,, J. Adams,, F. Gertler,, R. Li,, and P. Cossart. 2004. The RickA protein of Rickettsia conorii activates the Arp2/3 complex. Nature 427: 457 461.PubMed CrossRef
55. Gouin, E.,, H. Gantelet,, C. Egile,, I. Lasa,, H. Ohayon,, V. Villiers,, P. Gounon,, P. J. Sansonetti,, and P. Cossart. 1999. A comparative study of the actin-based motilities of the pathogenic bacteria Listeria monocytogenes, Shigella flexneri and Rickettsia conorii. J. Cell Sci. 112: 1697 1708.PubMed
56. Gouin, E.,, M. D. Welch,, and P. Cossart. 2005. Actin-based motility of intracellular pathogens. Curr. Opin. Microbiol. 8: 35 45.PubMed CrossRef
57. Hackstadt, T. 1996. The biology of rickettsiae. Infect. Agents Dis. 5: 127 143.PubMed
58. Haglund, C. M.,, J. E. Choe,, C. T. Skau,, D. R. Kovar,, and M. D. Welch. 2010. Rickettsia Sca2 is a bacterial formin-like mediator of actin-based motility. Nat. Cell Biol. 12: 1057 1063.PubMed CrossRef
59. Haider, A.,, R. Olszanecki,, R. Gryglewski,, M. L. Schwartzman,, E. Lianos,, A. Kappas,, A. Nasjletti,, and N. G. Abraham. 2002. Regulation of cyclooxygenase by the heme-heme oxygenase system in microvessel endothelial cells. J. Pharmacol. Exp. Ther. 300: 188 194.PubMed CrossRef
60. Harlander, R. S.,, M. Way,, Q. Ren,, D. Howe,, S. S. Grieshaber,, and R. A. Heinzen. 2003. Effects of ectopically expressed neuronal Wiskott-Aldrich syndrome protein domains on Rickettsia rickettsii actin-based motility. Infect. Immun. 71: 1551 1556.PubMed CrossRef
61. Hayden, M. S.,, and S. Ghosh. 2008. Shared principles in NF-κB signaling. Cell 132: 344 362.PubMed CrossRef
62. Heinzen, R. A.,, S. F. Hayes,, M. G. Peacock,, and T. Hackstadt. 1993. Directional actin polymerization associated with spotted fever group Rickettsia infection of Vero cells. Infect. Immun. 61: 1926 1935.PubMed
63. Iwasaki, H.,, F. Mahara,, N. Takada,, H. Fujita,, and T. Ueda. 2001. Fulminant Japanese spotted fever associated with hypercytokinemia. J. Clin. Microbiol. 39: 2341 2343.PubMed PubMed
64. Jeng, R. L.,, E. D. Goley,, J. A. D‘Alessio,, O. Y. Chaga,, T. M. Svitkina,, G. G. Borisy,, R. A. Heinzen,, and M. D. Welch. 2004. A Rickettsia WASP-like protein activates the Arp2/3 complex and mediates actin-based motility. Cell. Microbiol. 6: 761 769.PubMed CrossRef
65. Jensenius, M.,, P. E. Fournier,, P. Kelly,, B. Myrvang,, and D. Raoult. 2003a. African tick bite fever. Lancet Infect. Dis. 3: 557 564.PubMed
66. Jensenius, M.,, P. E. Fournier,, and D. Raoult. 2004. Rickettsioses and the international traveler. Clin. Infect. Dis. 39: 1493 1499.PubMed CrossRef
67. Jensenius, M.,, T. Ueland,, P. E. Fournier,, F. Brosstad,, E. Stylianou,, S. Vene,, B. Myrvang,, D. Raoult,, and P. Aukrust. 2003b. Systemic inflammatory responses in African tick-bite fever. J. Infect. Dis. 187: 1332 1336.PubMed CrossRef
68. Jordan, J. M.,, M. E. Woods,, H. M. Feng,, L. Soong,, and D. H. Walker. 2007. Rickettsiae-stimulated dendritic cells mediate protection against lethal rickettsial challenge in an animal model of spotted fever rickettsiosis. J. Infect. Dis. 196: 629 638.PubMed CrossRef
69. Jordan, J. M.,, M. E. Woods,, J. Olano,, and D. H. Walker. 2008. Absence of TLR4 signaling in C3H/HeJ mice predisposes to overwhelming rickettsial infection and decreased protective Th1 responses. Infect. Immun. 76: 3717 3724.PubMed CrossRef
70. Jordan, J. M.,, M. E. Woods,, L. Soong,, and D. H. Walker. 2009. Rickettsiae stimulate dendritic cells through Toll-like receptor 4, leading to enhanced NK cell activation in vivo. J. Infect. Dis. 199: 236 242.PubMed CrossRef
71. Joshi, S. G.,, C. W. Francis,, D. J. Silverman,, and S. K. Sahni. 2003. Nuclear factor-κB protects against host cell apoptosis during Rickettsia rickettsii infection by inhibiting activation of apical and effector caspases and maintaining mitochondrial integrity. Infect. Immun. 71: 4127 4136.PubMed CrossRef
72. Joshi, S. G.,, C. W. Francis,, D. J. Silverman,, and S. K. Sahni. 2004. NF-κB activation suppresses host cell apoptosis during Rickettsia rickettsii infection via regulatory effects on intracellular localization or levels of apoptogenic and anti-apoptotic proteins. FEMS Microbiol. Lett. 234: 333 341.PubMed CrossRef
73. Kaplanski, G. N.,, N. Teysseire,, C. Farnarier,, S. Kaplanski,, J.-C. Lissitzky,, J.-M. Durand,, J. Soubeyrand,, C. A. Dinarello,, and P. Bongrand. 1995. IL-6 and IL-8 production from cultured human endothelial cells stimulated by infection with Rickettsia conorii via a cell-associated IL-1α-dependent pathway. J. Clin. Invest. 96: 2839 2844.PubMed CrossRef
74. Kawai, T.,, and S. Akira. 2006. TLR signaling. Cell Death Differ. 13: 816 825.
75. Kawamura, K.,, K. Ishikawa,, Y. Wada,, S. Kimura,, H. Matsumoto,, T. Kohro,, H. Itabe,, T. Kodama,, and Y. Maruyama. 2005. Bilirubin from heme oxygenase-1 attenuates vascular endothelial activation and dysfunction. Arterioscler. Thromb. Vasc. Biol. 25: 155 160.PubMed CrossRef
76. Kimura, A.,, T. Naka,, T. Muta,, O. Takeuchi,, S. Akira,, I. Kawase,, and T. Kishimoto. 2005. Suppressor of cytokine signaling-1 selectively inhibits LPS-induced IL-6 production by regulating JAK-STAT. Proc. Natl. Acad. Sci. USA 102: 17089 17094.PubMed CrossRef
77. Kleba, B.,, T. R. Clark,, E. I. Lutter,, D. W. Ellison,, and T. Hackstadt. 2010. Disruption of the Rickettsia rickettsii Sca2 autotransporter inhibits actin-based motility. Infect. Immun. 78: 2240 2247.PubMed CrossRef
78. Kluck, R. M.,, E. Bossy-Wetzel,, D. R. Green,, and D. D. Newmeyer. 1997. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 275: 1132 1136.PubMed CrossRef
79. Knipe, L.,, A. Meli,, L. Hewlett,, R. Bierings,, J. Dempster,, P. Skehel,, M. J. Hannah,, and T. Carter. 2010. A revised model for the secretion of tPA and cytokines from cultured endothelial cells. Blood 116: 2183 2191.PubMed CrossRef
80. Krishnaswamy, G.,, J. Kelley,, L. Yerra,, J. K. Smith,, and D. S. Chi. 1999. Human endothelium as a source of multifunctional cytokines: molecular regulation and possible role in human disease. J. Interferon Cytokine Res. 19: 91 104.PubMed
81. Kushida, T.,, G. L. Volti,, S. Quan,, A. Goodman,, and N. G. Abraham. 2002. Role of human heme oxygenase-1 in attenuating TNF-α-mediated inflammation injury in endothelial cells. J. Cell. Biochem. 87: 377 385.PubMed CrossRef
82. Li, H.,, T. R. Jerrells,, G. L. Spitalny,, and D. H. Walker. 1987. Gamma interferon as a crucial host defense against Rickettsia conorii in vivo. Infect. Immun. 55: 1252 1255.PubMed
83. Mahara, F. 1997. Japanese spotted fever: report of 31 cases and review of the literature. Emerg. Infect. Dis. 3: 105 111.PubMed CrossRef
84. Maines, M. D.,, and P. E. Gibbs. 2005. 30 some years of heme oxygenase: from a “molecular wrecking ball” to a “mesmerizing” trigger of cellular events. Biochem. Biophys. Res. Commun. 338: 568 577.PubMed CrossRef
85. Manca, C.,, L. Tsenova,, S. Freeman,, A. K. Barczak,, M. Tovey,, P. J. Murray,, C. Barry,, and G. Kaplan. 2005. Hypervirulent Mycobacterium tuberculosis W/Beijing strains upregulate type I IFNs and increase expression of negative regulators of the Jak-Stat pathway. J. Interferon Cytokine Res. 25: 694 701.PubMed CrossRef
86. Manor, E.,, and I. Sarov. 1990. Inhibition of Rickettsia conorii growth by recombinant tumor necrosis factor alpha: enhancement of inhibition by gamma interferon. Infect. Immun. 58: 1886 1890.PubMed
87. Mark, K. S.,, W. J. Trickler,, and D. W. Miller. 2001. Tumor necrosis factor-α induces cyclooxygenase-2 expression and prostaglandin release in brain microvessel endothelial cells. J. Pharmacol. Exp. Ther. 297: 1051 1058.PubMed
88. Martinez, J. J.,, S. Seveau,, E. Veiga,, S. Matsuyama,, and P. Cossart. 2005. Ku70, a component of DNA-dependent protein kinase, is a mammalian receptor for Rickettsia conorii. Cell 123: 1013 1023.PubMed CrossRef
89. McAllister, S. C.,, S. G. Hansen,, R. A. Ruhl,, C. M. Raggo,, V. R. DeFilippis,, D. Greenspan,, K. Fruh,, and A. V. Moses. 2004. Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression and activity in KSHV-infected endothelial cells. Blood 103: 3465 3473.PubMed CrossRef
90. McLeod, M. P.,, X. Qin,, S. E. Karpathy,, J. Gioia,, S. K. Highlander,, G. E. Fox,, T. Z. McNeill,, H. Jiang,, D. Muzny,, L. S. Jacob,, A. C. Hawes,, E. Sodergren,, R. Gill,, J. Hume,, M. Morgan,, G. Fan,, A. G. Amin,, R. A. Gibbs,, C. Hong,, X. J. Yu,, D. H. Walker,, and G. M. Weinstock. 2004. Complete genome sequence of Rickettsia typhi and comparison with sequences of other rickettsiae. J. Bacteriol. 186: 5842 5855.PubMed CrossRef
91. Mercurio, F.,, H. Zhu,, B. W. Murray,, A. Shevchenko,, B. L. Bennett,, J. Li,, D. B. Young,, M. Barbosa,, M. Mann,, A. Manning,, and A. Rao. 1997. IKK-1 and IKK-2: cytokine-activated IκB kinases essential for NF-κB activation. Science 278: 860 866.PubMed CrossRef
92. Mouffok, N.,, P. Parola,, H. Lepidi,, and D. Raoult. 2009. Mediterranean spotted fever in Algeria—new trends. Int. J. Infect. Dis. 13: 227 235.PubMed CrossRef
93. Muller, C.,, J. Paupert,, S. Monferran,, and B. Salles. 2005. The double life of the Ku protein: facing the DNA breaks and the extracellular environment. Cell Cycle 4: 438 441.PubMed
94. Nakagawa, R.,, T. Naka,, H. Tsutsui,, M. Fujimoto,, A. Kimura,, T. Abe,, E. Seki,, S. Sato,, O. Takeuchi,, K. Takeda,, S. Akira,, K. Yamanishi,, I. Kawase,, K. Nakanishi,, and T. Kishimoto. 2002. SOCS-1 participates in negative regulation of LPS responses. Immunity 17: 677 687.PubMed CrossRef
95. Nicholson, W. L.,, K. E. Allen,, J. H. McQuiston,, E. B. Breitschwerdt,, and S. E. Little. 2010. The increasing recognition of rickettsial pathogens in dogs and people. Trends Parasitol. 26: 205 212.PubMed CrossRef
96. Olano, J. P. 2005. Rickettsial infections. Ann. N. Y. Acad. Sci. 1063: 187 196.
97. Paddock, C. D. 2005. Rickettsia parkeri as a paradigm for multiple causes of tick-borne spotted fever in the Western Hemisphere. Ann N. Y. Acad. Sci. 1063: 315 326.PubMed CrossRef
98. Pang, H.,, and H. H. Winkler. 1994. Analysis of the peptidoglycan of Rickettsia prowazekii. J. Bacteriol. 176: 923 926.PubMed
99. Pham, C. G.,, C. Bubici,, F. Zazzeroni,, S. Papa,, J. Jones,, K. Alvarez,, S. Jayawardena,, E. De Smaele,, R. Cong,, C. Beaumont,, F. M. Torti,, S. V. Torti,, and G. Franzoso. 2004. Ferritin heavy chain upregulation by NF-κB inhibits TNFα-induced apoptosis by suppressing reactive oxygen species. Cell 119: 529 542.PubMed CrossRef
100. Radulovic, S.,, P. W. Price,, M. S. Beier,, J. Gaywee,, K. A. Macaluso,, and A. Azad. 2002. Rickettsia-macrophage interactions: host cell responses to Rickettsia akari and Rickettsia typhi. Infect. Immun. 70: 2576 2582.PubMed CrossRef
101. Radulovic, S.,, J. M. Troyer,, M. S. Beier,, A. O. Lau,, and A. F. Azad. 1999. Identification and molecular analysis of the gene encoding Rickettsia typhi hemolysin. Infect. Immun. 67: 6104 6108.PubMed
102. Raoult, D.,, O. Dutour,, L. Houhamdi,, R. Jankauskas,, P. E. Fournier,, Y. Ardagna,, M. Drancourt,, M. Signoli,, V. D. La,, Y. Macia,, and G. Aboudharam. 2006. Evidence for louse-transmitted diseases in soldiers of Napoleon’s Grand Army in Vilnius. J. Infect. Dis. 193: 112 120.PubMed CrossRef
103. Raoult, D.,, and C. D. Paddock. 2005. Rickettsia parkeri infection and other spotted fevers in the United States. N. Engl. J. Med. 353: 626 627.PubMed CrossRef
104. Raoult, D.,, T. Woodward,, and J. S. Dumler. 2004. The history of epidemic typhus. Infect. Dis. Clin. North Am. 18: 127 140.PubMed CrossRef
105. Rincón, M.,, and R. J. Davis. 2009. Regulation of the immune response by stress-activated protein kinases. Immunol. Rev. 228: 212 224.PubMed CrossRef
106. Rothwarf, D. M.,, E. Zandi,, G. Natoli,, and M. Karin. 1998. IKKγ is an essential regulatory subunit of the IκB kinase complex. Nature 395: 297 300.PubMed CrossRef
107. Roux, P. P.,, and J. Blenis. 2004. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol. Mol. Biol. Rev. 68: 320 344.PubMed CrossRef
108. Rovery, C.,, P. Brouqui,, and D. Raoult. 2008. Questions on Mediterranean spotted fever a century after its discovery. Emerg. Infect. Dis. 14: 1360 1367.PubMed CrossRef
109. Rydkina, E.,, A. Sahni,, R. B. Baggs,, D. J. Silverman,, and S. K. Sahni. 2006. Infection of human endothelial cells with spotted fever group rickettsiae stimulates cyclooxygenase-2 expression and release of prostaglandins. Infect. Immun. 74: 5067 5074.PubMed CrossRef
110. Rydkina, E.,, A. Sahni,, D. J. Silverman,, and S. ?K. Sahni. 2002. Rickettsia rickettsii infection of cultured human endothelial cells induces heme oxygenase 1 expression. Infect. Immun. 70: 4045 4052.PubMed
111. Rydkina, E.,, A. Sahni,, D. J. Silverman,, and S. K. Sahni. 2007. Comparative analysis of host cell signaling mechanisms activated in response to infection with Rickettsia conorii and Rickettsia typhi. J. Med. Microbiol. 56: 896 906.PubMed CrossRef
112. Rydkina, E.,, S. K. Sahni,, L. A. Santucci,, L. C. Turpin,, R. B. Baggs,, and D. J. Silverman. 2004. Selective modulation of antioxidant enzyme activities in host tissues during Rickettsia conorii infection. Microb. Pathog. 36: 293 301.PubMed CrossRef
113. Rydkina, E.,, D. J. Silverman,, and S. K. Sahni. 2005. Activation of p38 stress-activated protein kinase during Rickettsia rickettsii infection of human endothelial cells: role in the induction of chemokine response. Cell. Microbiol. 7: 1519 1530.PubMed CrossRef
114. Rydkina, E.,, L. C. Turpin,, and S. K. Sahni. 2008. Activation of p38 MAP kinase module facilitates in vitro host cell invasion by Rickettsia rickettsii. J. Med. Microbiol. 57: 1172 1175.PubMed CrossRef
115. Rydkina, E.,, L. C. Turpin,, D. J. Silverman,, and S. K. Sahni. 2009. Rickettsia rickettsii infection of human pulmonary microvascular endothelial cells: modulation of cyclooxygenase-2 expression. Clin. Microbiol. Infect. 15( Suppl. 2): 300 302.PubMed CrossRef
116. Sahni, S. K. 2007. Endothelial cell infection and hemostasis. Thromb. Res. 119: 531 549.PubMed CrossRef
117. Sahni, S. K.,, S. Kiriakidi,, P. M. Colonne,, A. Sahni,, and D. J. Silverman. 2009. Selective activation of signal transducer and activator of transcription (STAT) proteins STAT1 and STAT3 in human endothelial cells infected with Rickettsia rickettsii. Clin. Microbiol. Infect. 15( Suppl. 2): 303 304.PubMed CrossRef
118. Sahni, S. K.,, and E. Rydkina. 2009. Host-cell interactions with pathogenic Rickettsia species. Future Microbiol. 4: 323 339.PubMed CrossRef
119. Sahni, S. K.,, E. Rydkina,, S. G. Joshi,, L. A. Sporn,, and D. J. Silverman. 2003. Interactions of Rickettsia rickettsii with endothelial nuclear factor-κB in a “cell-free” system. Ann. N. Y. Acad. Sci. 990: 635 641.PubMed
120. Sahni, S. K.,, D. J. Van Antwerp,, M. E. Eremeeva,, D. J. Silverman,, V. J. Marder,, and L. A. Sporn. 1998. Proteasome-independent activation of nuclear factor κB in cytoplasmic extracts from human endothelial cells by Rickettsia rickettsii. Infect. Immun. 66: 1827 1833.PubMed
121. Schmaier, A. H.,, S. Srikanth,, M. T. Elghetany,, D. Normolle,, S. Gokhale,, H.-M. Feng,, and D. H. Walker. 2001. Hemostatic/fibrinolytic protein changes in C3H/HeN mice infected with Rickettsia conorii. A model for Rocky Mountain spotted fever. Thromb. Haemost. 86: 871 879.PubMed
122. Scorrano, L.,, and S. J. Korsmeyer. 2003. Mechanisms of cytochrome c release by proapoptotic Bcl-2 family members. Biochem. Biophys. Res. Commun. 304: 437 444.PubMed
123. Serio, A. W.,, R. L. Jeng,, C. M. Haglund,, S. C. Reed,, and M. D. Welch. 2010. Defining a core set of actin cytoskeletal proteins critical for actin-based motility of Rickettsia. Cell Host Microbe 7: 388 398.PubMed CrossRef
124. Sessler, C. N.,, M. Schwartz,, A. C. Windsor,, and A. A. Fowler III. 1995. Increased serum cytokines and intercellular adhesion molecule-1 in fulminant Rocky Mountain spotted fever. Crit. Care Med. 23: 973 976.PubMed
125. Shi, R.-J.,, P. J. Simpson-Haidaris,, V. J. Marder,, D. J. Silverman,, and L. A. Sporn. 2000. Post-transcriptional regulation of endothelial cell plasminogen activator inhibitor-1 expression during Rickettsia rickettsii infection. Microb. Pathog. 28: 127 133.PubMed CrossRef
126. Silverman, D. J. 1986. Adherence of platelets to human endothelial cells infected by Rickettsia rickettsii. J. Infect. Dis. 153: 694 700.PubMed CrossRef
127. Silverman, D. J.,, and S. B. Bond. 1984. Infection of human vascular endothelial cells by Rickettsia rickettsii. J. Infect. Dis. 149: 201 206.PubMed CrossRef
128. Smith, W. L.,, D. L. DeWitt,, and R. M. Garavito. 2000. Cyclooxygenases: structural, cellular, and molecular biology. Annu. Rev. Biochem. 69: 145 182.PubMed CrossRef
129. Soares, M. P.,, M. P. Seldon,, I. P. Gregoire,, T. Vassilevskaia,, P. O. Berberat,, J. Yu,, T.-Y. Tsui,, and F. H. Bach. 2004. Heme-oxygenase-1 modulates the expression of adhesion molecules associated with endothelial cell activation. J. Immunol. 172: 3553 3563.PubMed
130. Spiecker, M.,, H. Darius,, and J. K. Liao. 2000. A functional role of IκB-ϵ in endothelial cell activation. J. Immunol. 164: 3316 3322.PubMed
131. Sporn, L. A.,, P. J. Haidaris,, R.-J. Shi,, Y. Nemerson,, D. J. Silverman,, and V. J. Marder. 1994. Rickettsia rickettsii infection of cultured human endothelial cells induces tissue factor expression. Blood 83: 1527 1534.PubMed
132. Sporn, L. A.,, S. O. Lawrence,, D. J. Silverman,, and V. J. Marder. 1993. E-selectin-dependent neutrophil adhesion to Rickettsia rickettsii-infected endothelial cells. Blood 81: 2406 2412.PubMed
133. Sporn, L. A.,, and V. J. Marder. 1996. Interleukin-1? production during Rickettsia rickettsii infection of cultured endothelial cells: Potential role in autocrine cell stimulation. Infect. Immun. 64: 1609 1613.PubMed
134. Sporn, L. A.,, S. K. Sahni,, N. B. Lerner,, V. J. Marder,, D. J. Silverman,, L. C. Turpin,, and A. L. Schwab. 1997. Rickettsia rickettsii infection of cultured human endothelial cells induces NF-κB activation. Infect. Immun. 65: 2786 2791.PubMed
135. Sporn, L. A.,, R.-J. Shi,, S. O. Lawrence,, D. J. Silverman,, and V. J. Marder. 1991. Rickettsia rickettsii infection of cultured endothelial cells induces release of large von Willebrand factor multimers from Weibel-Palade bodies. Blood 78: 2595 2602.PubMed
136. Stevens, J. M.,, E. E. Galyov,, and M. P. Stevens. 2006. Actin-dependent movement of bacterial pathogens. Nat. Rev. Microbiol. 4: 91 101.PubMed CrossRef
137. Stocker, R.,, and J. F. Keaney, Jr. 2004. Role of oxidative modifications in atherosclerosis. Physiol. Rev. 84: 1381 1478.PubMed CrossRef
138. Sumbayev, V. V.,, and I. M. Yasinska. 2006. Role of MAP kinase-dependent apoptotic pathway in innate immune responses and viral infection. Scand. J. Immunol. 63: 391 400.PubMed CrossRef
139. Tak, P. P.,, and G. S. Firestein. 2001. NF-κB: a key role in inflammatory diseases. J. Clin. Invest. 107: 7 11.PubMed CrossRef
140. Tak, P. P.,, D. M. Gerlag,, K. R. Aupperle,, D. A. Van De Geest,, M. Overbeek,, B. L. Bennett,, D. L. Boyle,, A. M. Manning,, and G. S. Firestein. 2001. Inhibitor of nuclear factor κB kinase β is a key regulator of synovial inflammation. Arthritis Rheum. 44: 1897 1907.PubMed CrossRef
141. Teysseire, N.,, D. Arnoux,, G. George,, J. Sampol,, and D. Raoult. 1992. von Willebrand factor release and thrombomodulin and tissue factor expression in Rickettsia conorii-infected endothelial cells. Infect. Immun. 60: 4388 4393.PubMed
142. Turco, J.,, and H. H. Winkler. 1984. Effect of mouse lymphokines and cloned mouse interferon-γ on the interaction of Rickettsia prowazekii with mouse macrophage-like RAW264.7 cells. Infect. Immun. 45: 303 308.PubMed
143. Turco, J.,, and H. H. Winkler. 1986. Gamma-interferon-induced inhibition of the growth of Rickettsia prowazekii in fibroblasts cannot be explained by the degradation of tryptophan or other amino acids. Infect. Immun. 53: 38 46.PubMed
144. Turco, J.,, and H. H. Winkler. 1989. Isolation of Rickettsia prowazekii with reduced sensitivity to gamma interferon. Infect. Immun. 57: 1765 1772.PubMed
145. Turco, J.,, and H. H. Winkler. 1990a. Interferon-α/β and Rickettsia prowazekii: induction and sensitivity. Ann. N. Y. Acad. Sci. 590: 168 186.PubMed CrossRef
146. Turco, J.,, and H. H. Winkler. 1990b. Selection of alpha/beta interferon- and gamma interferon-resistant rickettsiae by passage of Rickettsia prowazekii in L929 cells. Infect. Immun. 58: 3279 3285.PubMed
147. Turco, J.,, and H. H. Winkler. 1991. Comparison of properties of virulent, avirulent, and interferon-resistant Rickettsia prowazekii strains. Infect. Immun. 59: 1647 1655.PubMed
148. Uchiya, K.,, and T. Nikai. 2005. Salmonella pathogenicity island 2-dependent expression of suppressor of cytokine signaling 3 in macrophages. Infect. Immun. 73: 5587 5594.PubMed CrossRef
149. Valbuena, G.,, W. Bradford,, and D. H. Walker. 2003. Expression analysis of the T-cell-targeting chemokines CXCL9 and CXCL10 in mice and humans with endothelial infections caused by rickettsiae of the spotted fever group. Am. J. Pathol. 163: 1357 1369.PubMed CrossRef
150. Valbuena, G.,, H. M. Feng,, and D. H. Walker. 2002. Mechanisms of immunity against rickettsiae. New perspectives and opportunities offered by unusual intracellular parasites. Microbes Infect. 4: 625 633.PubMed
151. Valbuena, G.,, J. M. Jordan,, and D. H. Walker. 2004. T cells mediate cross-protective immunity between spotted fever group rickettsiae and typhus group rickettsiae. J. Infect. Dis. 190: 1221 1227.PubMed CrossRef
152. Valbuena, G.,, and D. H. Walker. 2004. Effect of blocking the CXCL9/10-CXCR3 chemokine system in the outcome of endothelial-target rickettsial infections. Am. J. Trop. Med. Hyg. 71: 393 399.PubMed
153. Valbuena, G.,, and D. H. Walker. 2005a. Expression of CX3CL1 (fractalkine) in mice with endothelial-target rickettsial infection of the spotted-fever group. Virchows Arch. 446: 21 27.PubMed CrossRef
154. Valbuena, G.,, and D. H. Walker. 2005b. Changes in the adherens junctions of human endothelial cells infected with spotted fever group rickettsiae. Virchows Arch. 446: 379 382.PubMed CrossRef
155. Valbuena, G.,, and D. H. Walker. 2009. Infection of the endothelium by members of the order Rickettsiales. Thromb. Haemost. 102: 1071 1079.PubMed CrossRef
156. Vitale, G.,, S. Mansueto,, G. Gambino,, C. Mocciaro,, A. Spinelli,, G. B. Rini,, M. Affronti,, N. Chifari,, C. La Russa,, S. Di Rosa,, P. Colletti,, C. Barbera,, M. La Rosa,, G. Di Bella,, V. Ferlazzo,, S. Milano,, P. D’Agostino,, and E. Cillari. 2001. The acute phase response in Sicilian patients with boutonneuse fever admitted to hospitals in Palermo, 1992-1997. J. Infect. 42: 33 39.PubMed CrossRef
157. Volti, G. L.,, F. Seta,, M. L. Schwartzman,, A. Nasjletti,, and N. G. Abraham. 2003. Heme oxygenase attenuates angiotensin II-mediated increase in cyclooxygenase-2 activity in human femoral endothelial cells. Hypertension 41: 715 719.PubMed CrossRef
158. von Loewenich, F. D.,, D. G. Scorpio,, U. Reischl,, J. S. Dumler,, and C. Bogdan. 2004. Control of Anaplasma phagocytophilum, an obligate intracellular pathogen, in the absence of inducible nitric oxide synthase, phagocyte NADPH oxidase, tumor necrosis factor, Toll-like receptor (TLR)2 and TLR4, or the TLR adaptor molecule MyD88. Eur. J. Immunol. 34: 1789 1797.PubMed CrossRef
159. Walker, D. H. 2003. Principles of the malicious use of infectious agents to create terror: reasons for concern for organisms of the genus Rickettsia. Ann. N. Y. Acad. Sci. 990: 739 742.PubMed CrossRef
160. Walker, D. H. 2006. Targeting Rickettsia. N. Engl. J. Med. 354: 1418 1420.PubMed CrossRef
161. Walker, D. H. 2007. Rickettsiae and rickettsial infections: the current state of knowledge. Clin. Infect. Dis. 45( Suppl. 1): S39 S44.PubMed CrossRef
162. Walker, D. H. 2009. The realities of biodefense vaccines against Rickettsia. Vaccine 27( Suppl. 4): D52 D55.PubMed CrossRef
163. Walker, D. H.,, H. M. Feng,, and V. L. Popov. 2001a. Rickettsial phospholipase A 2 as a pathogenic mechanism in a model of cell injury by typhus and spotted fever group rickettsiae. Am. J. Trop. Med. Hyg. 65: 936 942.PubMed
164. Walker, D. H.,, S. D. Hudnall,, W. K. Szaniawski,, and H. M. Feng. 1999. Monoclonal antibody-based immunohistochemical diagnosis of rickettsialpox: the macrophage is the principal target. Mod. Pathol. 12: 529 533.PubMed
165. Walker, D. H.,, and N. Ismail. 2008. Emerging and re-emerging rickettsioses: endothelial cell infection and early disease events. Nat. Rev. Microbiol. 6: 375 386.PubMed CrossRef
166. Walker, D. H.,, and N. H. Kirkman. 1980. Rocky Mountain spotted fever and deficiency in glucose-6-phosphate dehydrogenase. J. Infect. Dis. 142: 771.PubMed CrossRef
167. Walker, D. H.,, J. P. Olano,, and H. M. Feng. 2001b. Critical role of cytotoxic T lymphocytes in immune clearance of rickettsial infection. Infect. Immun. 69: 1841 1846.PubMed CrossRef
168. Walker, D. H.,, C. D. Paddock,, and J. S. Dumler. 2008. Emerging and re-emerging tick-transmitted rickettsial and ehrlichial infections. Med. Clin. North Am. 92: 1345 1361.PubMed CrossRef
169. Walker, D. H.,, V. L. Popov,, and H. M. Feng. 2000. Establishment of a novel endothelial target mouse model of a typhus group rickettsiosis: evidence for critical roles for gamma interferon and CD8 T lymphocytes. Lab. Invest. 80: 1361 1372.PubMed
170. Walker, D. H.,, V. L. Popov,, J. Wen,, and H. M. Feng. 1994. Rickettsia conorii infection of C3H/HeN mice. A model of endothelial-target rickettsiosis. Lab. Invest. 70: 358 368.PubMed
171. Walker, D. H.,, and X. J. Yu. 2005. Progress in rickettsial genome analysis from pioneering of Rickettsia prowazekii to the recent Rickettsia typhi. Ann. N. Y. Acad. Sci. 1063: 13 25.PubMed CrossRef
172. Walker, T. S. 1984. Rickettsial interactions with human endothelial cells in vitro: adherence and entry. Infect. Immun. 44: 205 210.PubMed
173. Walker, T. S.,, J. S. Brown,, C. S. Hoover,, and D. A. Morgan. 1990. Endothelial prostaglandin secretion: effects of typhus rickettsiae. J. Infect. Dis. 162: 1136 1144.PubMed CrossRef
174. Walker, T. S.,, M. W. Dersch,, and W. E. White. 1991. Effects of typhus rickettsiae on peritoneal and alveolar macrophages: rickettsiae stimulate leukotriene and prostaglandin secretion. J. Infect. Dis. 163: 568 573.PubMed CrossRef
175. Walker, T. S.,, and C. S. Hoover. 1991. Rickettsial effects on leukotriene and prostaglandin secretion by mouse polymorphonuclear leukocytes. Infect. Immun. 59: 351 356.PubMed
176. Walker, T. S.,, and G. E. Mellott. 1993. Rickettsial stimulation of endothelial platelet-activating factor synthesis. Infect. Immun. 61: 2024 2029.PubMed
177. Whelton, A.,, J. V. Donadio, Jr.,, and B. L. Elisberg. 1968. Acute renal failure complicating rickettsial infections in glucose-6-phosphate dehydrogenase deficient individuals. Ann. Intern. Med. 69: 323 328.PubMed
178. Whitworth, T.,, V. L. Popov,, X. J. Yu,, D. H. Walker,, and D. H. Bouyer. 2005. Expression of the Rickettsia prowazekii pld or tlyC gene in Salmonella enterica serovar Typhimurium mediates phagosomal escape. Infect. Immun. 73: 6668 6673.PubMed CrossRef
179. Woods, M. E.,, and J. P. Olano. 2008. Host defenses to Rickettsia rickettsii infection contribute to increased microvascular permeability in human cerebral endothelial cells. J. Clin. Immunol. 28: 174 185.PubMed CrossRef
180. Woodward, T. E. 1973. A historical account of the rickettsial diseases with a discussion of unsolved problems. J. Infect. Dis. 127: 583 594.PubMed CrossRef
181. Yachie, A.,, Y. Niida,, T. Wada,, N. Igarashi,, H. Kaneda,, T. Toma,, K. Ohta,, Y. Kasahara,, and S. Koizumi. 1999. Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J. Clin. Invest. 103: 129 135.PubMed CrossRef
182. Yamada, N.,, M. Yamaya,, S. Okinaga,, M. Terajima,, R. Lee,, T. Suzuki,, K. Sekizawa,, H. Suzuki,, and H. Sasaki. 1997. Heme oxygenase I inhibits rhinovirus type 14 (HRV-14) infection and replication by cultured human tracheal epithelium. Am. J. Respir. Crit. Care Med. 155: A943.
183. Zandi, E.,, D. M. Rothwarf,, M. Delhase,, M. Hayakawa,, and M. Karin. 1997. The IκB kinase complex (IKK) contains two kinase subunits, IKKα and IKKβ, necessary for IκB phosphorylation and NF-κB activation. Cell 91: 243 252.PubMed CrossRef
184. Zhou, H.,, F. Lu,, C. Latham,, D. S. Zander,, and G. A. Visner. 2004. Heme oxygenase-1 expression in human lungs with cystic fibrosis and cytoprotective effects against Pseudomonas aeruginosa in vitro. Am. J. Respir. Crit. Care Med. 170: 633 640.PubMed CrossRef

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error