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

Key Concept Ranking

Rocky Mountain Spotted Fever
Tumor Necrosis Factor alpha
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 36:18961900.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 396:133140.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. 8:597606.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. 13:197204.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 6:160167.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. 18:655660.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. 286:257262.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 99:1609316098.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):249250.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. 3:223236.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. 197:142147.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 cIAP2-independent mechanism. J. Infect. Dis. 199:13891398.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. 65:5256.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. 51:341352.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. 192:10151025.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 103:761766.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. 214:136148.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. 9:15861597.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. 189:19211925.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. 174:10511057.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 95:46464651.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: 155165.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. 295:267278.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. 177:26992706.PubMed
25. Dantas-Torres, F. 2007. Rocky Mountain spotted fever. Lancet Infect. Dis. 7:724732.PubMed CrossRef
26. Davidge, S. T. 2001. Prostaglandin H synthase and vascular function. Circ. Res. 89:650660.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 38:452459.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. 6:423429. (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. 353:587594.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. 276:2845128458.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. 198:576585.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. 196:770781.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 388:548554.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. 175:11421152.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. 58:24592463.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. 590:3950.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. 77:32443248.PubMed CrossRef
38. Dumler, J. S.,, and D. H. Walker. 2005. Rocky Mountain spotted fever—changing ecology and persisting virulence. N. Engl. J. Med. 353:551553.PubMed CrossRef
39. Dyer, L. A.,, and C. Patterson. 2010. Development of the endothelium: an emphasis on heterogeneity. Semin. Thromb. Hemost. 36:227235.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. 479516. 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. 8:788796.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. 128144. 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 144:20372048.PubMed CrossRef
44. Esposti, M. D. 2002. The roles of Bid. Apoptosis 7:433440.PubMed CrossRef
45. Fan, H.,, and J. A. Cook. 2004. Molecular mechanisms of endotoxin tolerance. J. Endotoxin Res. 10:7184.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. 2:373377.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. 75:31123123.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. 62:19521960.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. 68:67296736.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. 72:35243530.PubMed CrossRef
51. Galley, H. F.,, and N. R. Webster. 2004. Physiology of the endothelium. Br. J. Anaesth. 93:105113.
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. 30:219223.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 427:457461.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. 112:16971708.PubMed
56. Gouin, E.,, M. D. Welch,, and P. Cossart. 2005. Actin-based motility of intracellular pathogens. Curr. Opin. Microbiol. 8:3545.PubMed CrossRef
57. Hackstadt, T. 1996. The biology of rickettsiae. Infect. Agents Dis. 5:127143.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. 12:10571063.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. 300:188194.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. 71:15511556.PubMed CrossRef
61. Hayden, M. S.,, and S. Ghosh. 2008. Shared principles in NF-κB signaling. Cell 132:344362.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. 61:19261935.PubMed
63. Iwasaki, H.,, F. Mahara,, N. Takada,, H. Fujita,, and T. Ueda. 2001. Fulminant Japanese spotted fever associated with hypercytokinemia. J. Clin. Microbiol. 39:23412343.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. 6:761769.PubMed CrossRef
65. Jensenius, M.,, P. E. Fournier,, P. Kelly,, B. Myrvang,, and D. Raoult. 2003a. African tick bite fever. Lancet Infect. Dis. 3:557564.PubMed
66. Jensenius, M.,, P. E. Fournier,, and D. Raoult. 2004. Rickettsioses and the international traveler. Clin. Infect. Dis. 39:14931499.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. 187:13321336.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. 196:629638.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. 76:37173724.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. 199:236242.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. 71:41274136.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. 234:333341.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. 96:28392844.PubMed CrossRef
74. Kawai, T.,, and S. Akira. 2006. TLR signaling. Cell Death Differ. 13:816825.
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. 25:155160.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 102:1708917094.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. 78:22402247.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 275:11321136.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 116:21832191.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. 19:91104.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. 87:377385.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. 55:12521255.PubMed
83. Mahara, F. 1997. Japanese spotted fever: report of 31 cases and review of the literature. Emerg. Infect. Dis. 3:105111.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. 338:568577.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. 25:694701.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. 58:18861890.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. 297:10511058.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 123:10131023.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 103:34653473.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. 186:58425855.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 278:860866.PubMed CrossRef
92. Mouffok, N.,, P. Parola,, H. Lepidi,, and D. Raoult. 2009. Mediterranean spotted fever in Algeria—new trends. Int. J. Infect. Dis. 13:227235.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 4:438441.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 17:677687.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. 26:205212.PubMed CrossRef
96. Olano, J. P. 2005. Rickettsial infections. Ann. N. Y. Acad. Sci. 1063:187196.
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. 1063:315326.PubMed CrossRef
98. Pang, H.,, and H. H. Winkler. 1994. Analysis of the peptidoglycan of Rickettsia prowazekii. J. Bacteriol. 176:923926.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 119:529542.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. 70:25762582.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. 67:61046108.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. 193:112120.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. 353:626627.PubMed CrossRef
104. Raoult, D.,, T. Woodward,, and J. S. Dumler. 2004. The history of epidemic typhus. Infect. Dis. Clin. North Am. 18:127140.PubMed CrossRef
105. Rincón, M.,, and R. J. Davis. 2009. Regulation of the immune response by stress-activated protein kinases. Immunol. Rev. 228:212224.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 395:297300.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. 68:320344.PubMed CrossRef
108. Rovery, C.,, P. Brouqui,, and D. Raoult. 2008. Questions on Mediterranean spotted fever a century after its discovery. Emerg. Infect. Dis. 14:13601367.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. 74:50675074.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. 70:40454052.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. 56:896906.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. 36:293301.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. 7:15191530.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. 57:11721175.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):300302.PubMed CrossRef
116. Sahni, S. K. 2007. Endothelial cell infection and hemostasis. Thromb. Res. 119:531549.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):303304.PubMed CrossRef
118. Sahni, S. K.,, and E. Rydkina. 2009. Host-cell interactions with pathogenic Rickettsia species. Future Microbiol. 4:323339.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. 990:635641.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. 66:18271833.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. 86:871879.PubMed
122. Scorrano, L.,, and S. J. Korsmeyer. 2003. Mechanisms of cytochrome c release by proapoptotic Bcl-2 family members. Biochem. Biophys. Res. Commun. 304:437444.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 7:388398.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. 23:973976.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. 28:127133.PubMed CrossRef
126. Silverman, D. J. 1986. Adherence of platelets to human endothelial cells infected by Rickettsia rickettsii. J. Infect. Dis. 153:694700.PubMed CrossRef
127. Silverman, D. J.,, and S. B. Bond. 1984. Infection of human vascular endothelial cells by Rickettsia rickettsii. J. Infect. Dis. 149:201206.PubMed CrossRef
128. Smith, W. L.,, D. L. DeWitt,, and R. M. Garavito. 2000. Cyclooxygenases: structural, cellular, and molecular biology. Annu. Rev. Biochem. 69:145182.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. 172:35533563.PubMed
130. Spiecker, M.,, H. Darius,, and J. K. Liao. 2000. A functional role of IκB-ϵ in endothelial cell activation. J. Immunol. 164:33163322.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 83:15271534.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 81:24062412.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. 64:16091613.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. 65:27862791.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 78:25952602.PubMed
136. Stevens, J. M.,, E. E. Galyov,, and M. P. Stevens. 2006. Actin-dependent movement of bacterial pathogens. Nat. Rev. Microbiol. 4:91101.PubMed CrossRef
137. Stocker, R.,, and J. F. Keaney, Jr. 2004. Role of oxidative modifications in atherosclerosis. Physiol. Rev. 84:13811478.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. 63:391400.PubMed CrossRef
139. Tak, P. P.,, and G. S. Firestein. 2001. NF-κB: a key role in inflammatory diseases. J. Clin. Invest. 107:711.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. 44:18971907.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. 60:43884393.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. 45:303308.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. 53:3846.PubMed
144. Turco, J.,, and H. H. Winkler. 1989. Isolation of Rickettsia prowazekii with reduced sensitivity to gamma interferon. Infect. Immun. 57:17651772.PubMed
145. Turco, J.,, and H. H. Winkler. 1990a. Interferon-α/β and Rickettsia prowazekii: induction and sensitivity. Ann. N. Y. Acad. Sci. 590:168186.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. 58:32793285.PubMed
147. Turco, J.,, and H. H. Winkler. 1991. Comparison of properties of virulent, avirulent, and interferon-resistant Rickettsia prowazekii strains. Infect. Immun. 59:16471655.PubMed
148. Uchiya, K.,, and T. Nikai. 2005. Salmonella pathogenicity island 2-dependent expression of suppressor of cytokine signaling 3 in macrophages. Infect. Immun. 73:55875594.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. 163:13571369.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. 4:625633.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. 190:12211227.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. 71:393399.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. 446:2127.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. 446:379382.PubMed CrossRef
155. Valbuena, G.,, and D. H. Walker. 2009. Infection of the endothelium by members of the order Rickettsiales. Thromb. Haemost. 102:10711079.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. 42:3339.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 41:715719.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. 34:17891797.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. 990:739742.PubMed CrossRef
160. Walker, D. H. 2006. Targeting Rickettsia. N. Engl. J. Med. 354:14181420.PubMed CrossRef
161. Walker, D. H. 2007. Rickettsiae and rickettsial infections: the current state of knowledge. Clin. Infect. Dis. 45(Suppl. 1):S39S44.PubMed CrossRef
162. Walker, D. H. 2009. The realities of biodefense vaccines against Rickettsia. Vaccine 27(Suppl. 4):D52D55.PubMed CrossRef
163. Walker, D. H.,, H. M. Feng,, and V. L. Popov. 2001a. Rickettsial phospholipase A2 as a pathogenic mechanism in a model of cell injury by typhus and spotted fever group rickettsiae. Am. J. Trop. Med. Hyg. 65:936942.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. 12:529533.PubMed
165. Walker, D. H.,, and N. Ismail. 2008. Emerging and re-emerging rickettsioses: endothelial cell infection and early disease events. Nat. Rev. Microbiol. 6:375386.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. 69:18411846.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. 92:13451361.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. 80:13611372.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. 70:358368.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. 1063:1325.PubMed CrossRef
172. Walker, T. S. 1984. Rickettsial interactions with human endothelial cells in vitro: adherence and entry. Infect. Immun. 44:205210.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. 162:11361144.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. 163:568573.PubMed CrossRef
175. Walker, T. S.,, and C. S. Hoover. 1991. Rickettsial effects on leukotriene and prostaglandin secretion by mouse polymorphonuclear leukocytes. Infect. Immun. 59:351356.PubMed
176. Walker, T. S.,, and G. E. Mellott. 1993. Rickettsial stimulation of endothelial platelet-activating factor synthesis. Infect. Immun. 61:20242029.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. 69:323328.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. 73:66686673.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. 28:174185.PubMed CrossRef
180. Woodward, T. E. 1973. A historical account of the rickettsial diseases with a discussion of unsolved problems. J. Infect. Dis. 127:583594.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. 103:129135.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 91:243252.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. 170:633640.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