Chapter 37 : Interplay between Myeloid Cells and Humoral Innate Immunity

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The immune system of mammalians is organized around two components: the innate immunity and the adaptive immunity. Older in terms of evolution, the innate immune system constitutes the first line of defense against microorganisms. This system is supplemented by the adaptive immunity, which is more recent in terms of evolution and provides the basis of immunological memory. Both the adaptive and innate immune systems are composed of a cellular and a humoral arm acting in a complementary and coordinated manner to regulate the innate response.

Citation: Jaillon S, Bonavita E, Garlanda C, Mantovani A. 2017. Interplay between Myeloid Cells and Humoral Innate Immunity, p 661-678. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0051-2016
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Figure 1

Humoral innate immunity. Soluble PRMs are expressed and secreted by a variety of cells, including in particular myeloid cells, allowing the production of PRMs over time. Some PRMs (e.g., PTX3, PGRP-S, and ficolin-1) are stored in neutrophil granules for rapid release in minutes. PRMs such as PTX3 and PGRP-S are also found among NET-associated molecules (NAMs). Production of PRMs by mononuclear phagocytes, dendritic cells, and endothelium in a gene expression-dependent manner sustains the presence of these molecules over time. Finally, epithelial tissues (e.g., liver) sustain systemic mass production.

Citation: Jaillon S, Bonavita E, Garlanda C, Mantovani A. 2017. Interplay between Myeloid Cells and Humoral Innate Immunity, p 661-678. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0051-2016
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Figure 2

Gene organization, protein structures, and roles of PTX3. The PTX3 gene is organized in three exons. The first two exons code for the signal peptide (SP) and the N-terminal domain of the protein (NTD), respectively, and the third exon codes for the pentraxin domain (PTX). A three-dimensional model of the pentraxin domain has been generated based on the crystallographic structures of CRP and SAP, showing that the pentraxin domain of PTX3 adopts a β-jelly roll topology. PTX3 has a unique quaternary structure with eight subunits, associated together to form an octamer by disulfide bonds between cysteine residues present on both the N-terminal and C-terminal domains. Once released, PTX3 plays a role in pathogen opsonization and agglutination, complement activation, regulation of inflammation and leukocyte recruitment, angiogenesis, extracellular matrix (ECM) remodeling, and wound healing. Men B, meningococcus type B; FGF, fibroblast growth factor 2; TSG-6, tumor necrosis factor-inducible gene 6 protein; IαI, inter-alpha-trypsin inhibitor.

Citation: Jaillon S, Bonavita E, Garlanda C, Mantovani A. 2017. Interplay between Myeloid Cells and Humoral Innate Immunity, p 661-678. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0051-2016
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Figure 3

Role of PTX3 in defense against fungi. In the presence of PTX3-opsonized conidia, FcγRIIA induces inside-out CD11b/CD18 activation, recruitment to the phagocytic cup, and amplification of C3b-opsonized conidia phagocytosis (left panel). PTX3 interacts with ficolin-2 and MBL on the surface of conidia and , respectively, triggering complement deposition and phagocytosis of pathogens.

Citation: Jaillon S, Bonavita E, Garlanda C, Mantovani A. 2017. Interplay between Myeloid Cells and Humoral Innate Immunity, p 661-678. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0051-2016
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1. Iwasaki A,, Medzhitov R . 2010. Regulation of adaptive immunity by the innate immune system. Science 327 : 291 295.
2. Bottazzi B,, Doni A,, Garlanda C,, Mantovani A . 2010. An integrated view of humoral innate immunity: pentraxins as a paradigm. Annu Rev Immunol 28 : 157 183.
3. Holmskov U,, Thiel S,, Jensenius JC . 2003. Collections and ficolins: humoral lectins of the innate immune defense. Annu Rev Immunol 21 : 547 578.
4. Gupta G,, Surolia A . 2007. Collectins: sentinels of innate immunity. BioEssays 29 : 452 464.
5. Henriksen ML,, Brandt J,, Andrieu JP,, Nielsen C,, Jensen PH,, Holmskov U,, Jorgensen TJ,, Palarasah Y,, Thielens NM,, Hansen S . 2013. Heteromeric complexes of native collectin kidney 1 and collectin liver 1 are found in the circulation with MASPs and activate the complement system. J Immunol 191 : 6117 6127.
6. Ohtani K,, Suzuki Y,, Eda S,, Kawai T,, Kase T,, Keshi H,, Sakai Y,, Fukuoh A,, Sakamoto T,, Itabe H,, Suzutani T,, Ogasawara M,, Yoshida I,, Wakamiya N . 2001. The membrane-type collectin CL-P1 is a scavenger receptor on vascular endothelial cells. J Biol Chem 276 : 44222 44228.
7. Nakamura K,, Funakoshi H,, Miyamoto K,, Tokunaga F,, Nakamura T . 2001. Molecular cloning and functional characterization of a human scavenger receptor with C-type lectin (SRCL), a novel member of a scavenger receptor family. Biochem Biophys Res Commun 280 : 1028 1035.
8. Ma YJ,, Hein E,, Munthe-Fog L,, Skjoedt MO,, Bayarri-Olmos R,, Romani L,, Garred P . 2015. Soluble collectin-12 (CL-12) is a pattern recognition molecule initiating complement activation via the alternative pathway. J Immunol 195 : 3365 3373.
9. Fujita T . 2002. Evolution of the lectin-complement pathway and its role in innate immunity. Nat Rev Immunol 2 : 346 353.
10. Matsushita M,, Matsushita A,, Endo Y,, Nakata M,, Kojima N,, Mizuochi T,, Fujita T . 2004. Origin of the classical complement pathway: lamprey orthologue of mammalian C1q acts as a lectin. Proc Natl Acad Sci U S A 101 : 10127 10131.
11. Sekine H,, Kenjo A,, Azumi K,, Ohi G,, Takahashi M,, Kasukawa R,, Ichikawa N,, Nakata M,, Mizuochi T,, Matsushita M,, Endo Y,, Fujita T . 2001. An ancient lectin-dependent complement system in an ascidian: novel lectin isolated from the plasma of the solitary ascidian, Halocynthia roretzi . J Immunol 167 : 4504 4510.
12. Katyal SL,, Singh G,, Locker J . 1992. Characterization of a second human pulmonary surfactant-associated protein SP-A gene. Am J Respir Cell Mol Biol 6 : 446 452.
13. Floros J,, Hoover RR . 1998. Genetics of the hydrophilic surfactant proteins A and D. Biochim Biophys Acta 1408 : 312 322.
14. Uemura T,, Sano H,, Katoh T,, Nishitani C,, Mitsuzawa H,, Shimizu T,, Kuroki Y . 2006. Surfactant protein A without the interruption of Gly-X-Y repeats loses a kink of oligomeric structure and exhibits impaired phospholipid liposome aggregation ability. Biochemistry 45 : 14543 14551.
15. Crouch E,, Persson A,, Chang D,, Heuser J . 1994. Molecular structure of pulmonary surfactant protein D (SP-D). J Biol Chem 269 : 17311 17319.
16. Kishore U,, Greenhough TJ,, Waters P,, Shrive AK,, Ghai R,, Kamran MF,, Bernal AL,, Reid KB,, Madan T,, Chakraborty T . 2006. Surfactant proteins SP-A and SP-D: structure, function and receptors. Mol Immunol 43 : 1293 1315.
17. Spissinger T,, Schäfer KP,, Voss T . 1991. Assembly of the surfactant protein SP-A. Deletions in the globular domain interfere with the correct folding of the molecule. Eur J Biochem 199 : 65 71.
18. Hansen S,, Holm D,, Moeller V,, Vitved L,, Bendixen C,, Reid KB,, Skjoedt K,, Holmskov U . 2002. CL-46, a novel collectin highly expressed in bovine thymus and liver. J Immunol 169 : 5726 5734.
19. Lipscombe RJ,, Sumiya M,, Summerfield JA,, Turner MW . 1995. Distinct physicochemical characteristics of human mannose binding protein expressed by individuals of differing genotype. Immunology 85 : 660 667.
20. Dahl MR,, Thiel S,, Matsushita M,, Fujita T,, Willis AC,, Christensen T,, Vorup-Jensen T,, Jensenius JC . 2001. MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway. Immunity 15 : 127 135.
21. Teillet F,, Dublet B,, Andrieu JP,, Gaboriaud C,, Arlaud GJ,, Thielens NM . 2005. The two major oligomeric forms of human mannan-binding lectin: chemical characterization, carbohydrate-binding properties, and interaction with MBL-associated serine proteases. J Immunol 174 : 2870 2877.
22. Jensenius H,, Klein DC,, van Hecke M,, Oosterkamp TH,, Schmidt T,, Jensenius JC . 2009. Mannan-binding lectin: structure, oligomerization, and flexibility studied by atomic force microscopy. J Mol Biol 391 : 246 259.
23. van de Wetering JK,, van Eijk M,, van Golde LM,, Hartung T,, van Strijp JA,, Batenburg JJ . 2001. Characteristics of surfactant protein A and D binding to lipoteichoic acid and peptidoglycan, 2 major cell wall components of gram-positive bacteria. J Infect Dis 184 : 1143 1151.
24. Drickamer K . 1992. Engineering galactose-binding activity into a C-type mannose-binding protein. Nature 360 : 183 186.
25. Madan T,, Kaur S,, Saxena S,, Singh M,, Kishore U,, Thiel S,, Reid KB,, Sarma PU . 2005. Role of collectins in innate immunity against aspergillosis. Med Mycol 43( Suppl 1) : S155 S163.
26. Allen MJ,, Voelker DR,, Mason RJ . 2001. Interactions of surfactant proteins A and D with Saccharomyces cerevisiae and Aspergillus fumigatus . Infect Immun 69 : 2037 2044.
27. Lin KW,, Jen KY,, Suarez CJ,, Crouch EC,, Perkins DL,, Finn PW . 2010. Surfactant protein D-mediated decrease of allergen-induced inflammation is dependent upon CTLA4. J Immunol 184 : 6343 6349.
28. Gowdy KM,, Cardona DM,, Nugent JL,, Giamberardino C,, Thomas JM,, Mukherjee S,, Martinu T,, Foster WM,, Plevy SE,, Pastva AM,, Wright JR,, Palmer SM . 2012. Novel role for surfactant protein A in gastrointestinal graft-versus-host disease. J Immunol 188 : 4897 4905.
29. Hartshorn KL,, Crouch EC,, White MR,, Eggleton P,, Tauber AI,, Chang D,, Sastry K . 1994. Evidence for a protective role of pulmonary surfactant protein D (SP-D) against influenza A viruses. J Clin Invest 94 : 311 319.
30. White MR,, Crouch E,, Vesona J,, Tacken PJ,, Batenburg JJ,, Leth-Larsen R,, Holmskov U,, Hartshorn KL . 2005. Respiratory innate immune proteins differentially modulate the neutrophil respiratory burst response to influenza A virus. Am J Physiol Lung Cell Mol Physiol 289 : L606 L616.
31. Reichhardt MP,, Meri S . 2016. SALSA: a regulator of the early steps of complement activation on mucosal surfaces. Front Immunol 7 : 85. doi:10.3389/fimmu.2016.00085.
32. Garred P,, Honoré C,, Ma YJ,, Munthe-Fog L,, Hummelshøj T . 2009. MBL2, FCN1, FCN2 and FCN3—the genes behind the initiation of the lectin pathway of complement. Mol Immunol 46 : 2737 2744.
33. Sørensen CM,, Hansen TK,, Steffensen R,, Jensenius JC,, Thiel S . 2006. Hormonal regulation of mannan-binding lectin synthesis in hepatocytes. Clin Exp Immunol 145 : 173 182.
34. Ezekowitz RA,, Day LE,, Herman GA . 1988. A human mannose-binding protein is an acute-phase reactant that shares sequence homology with other vertebrate lectins. J Exp Med 167 : 1034 1046.
35. Arai T,, Tabona P,, Summerfield JA . 1993. Human mannose-binding protein gene is regulated by interleukins, dexamethasone and heat shock. Q J Med 86 : 575 582.
36. Thiel S,, Holmskov U,, Hviid L,, Laursen SB,, Jensenius JC . 1992. The concentration of the C-type lectin, mannan-binding protein, in human plasma increases during an acute phase response. Clin Exp Immunol 90 : 31 35.
37. Perez-Castellano M,, Peñaranda M,, Payeras A,, Milà J,, Riera M,, Vidal J,, Pujalte F,, Pareja A,, Villalonga C,, Matamoros N . 2006. Mannose-binding lectin does not act as an acute-phase reactant in adults with community-acquired pneumococcal pneumonia. Clin Exp Immunol 145 : 228 234.
38. Dean MM,, Minchinton RM,, Heatley S,, Eisen DP . 2005. Mannose binding lectin acute phase activity in patients with severe infection. J Clin Immunol 25 : 346 352.
39. Nonaka M,, Imaeda H,, Matsumoto S,, Yong Ma B,, Kawasaki N,, Mekata E,, Andoh A,, Saito Y,, Tani T,, Fujiyama Y,, Kawasaki T . 2014. Mannan-binding protein, a C-type serum lectin, recognizes primary colorectal carcinomas through tumor-associated Lewis glycans. J Immunol 192 : 1294 1301.
40. Fujita T,, Matsushita M,, Endo Y . 2004. The lectin-complement pathway—its role in innate immunity and evolution. Immunol Rev 198 : 185 202.
41. Thielens NM . 2011. The double life of M-ficolin: what functions when circulating in serum and tethered to leukocyte surfaces? J Leukoc Biol 90 : 410 412.
42. Ren Y,, Ding Q,, Zhang X . 2014. Ficolins and infectious diseases. Virol Sin 29 : 25 32.
43. Matsushita M . 2010. Ficolins: complement-activating lectins involved in innate immunity. J Innate Immun 2 : 24 32.
44. Lacroix M,, Dumestre-Pérard C,, Schoehn G,, Houen G,, Cesbron JY,, Arlaud GJ,, Thielens NM . 2009. Residue Lys57 in the collagen-like region of human L-ficolin and its counterpart Lys47 in H-ficolin play a key role in the interaction with the mannan-binding lectin-associated serine proteases and the collectin receptor calreticulin. J Immunol 182 : 456 465.
45. Endo Y,, Matsushita M,, Fujita T . 2007. Role of ficolin in innate immunity and its molecular basis. Immunobiology 212 : 371 379.
46. Ma YG,, Cho MY,, Zhao M,, Park JW,, Matsushita M,, Fujita T,, Lee BL . 2004. Human mannose-binding lectin and L-ficolin function as specific pattern recognition proteins in the lectin activation pathway of complement. J Biol Chem 279 : 25307 25312.
47. Lynch NJ,, Roscher S,, Hartung T,, Morath S,, Matsushita M,, Maennel DN,, Kuraya M,, Fujita T,, Schwaeble WJ . 2004. L-Ficolin specifically binds to lipoteichoic acid, a cell wall constituent of Gram-positive bacteria, and activates the lectin pathway of complement. J Immunol 172 : 1198 1202.
48. Luo F,, Sun X,, Wang Y,, Wang Q,, Wu Y,, Pan Q,, Fang C,, Zhang XL . 2013. Ficolin-2 defends against virulent Mycobacteria tuberculosis infection in vivo, and its insufficiency is associated with infection in humans. PLoS One 8 : e73859. doi:10.1371/journal.pone.0073859.
49. Liu J,, Ali MA,, Shi Y,, Zhao Y,, Luo F,, Yu J,, Xiang T,, Tang J,, Li D,, Hu Q,, Ho W,, Zhang X . 2009. Specifically binding of L-ficolin to N-glycans of HCV envelope glycoproteins E1 and E2 leads to complement activation. Cell Mol Immunol 6 : 235 244.
50. Verma A,, White M,, Vathipadiekal V,, Tripathi S,, Mbianda J,, Ieong M,, Qi L,, Taubenberger JK,, Takahashi K,, Jensenius JC,, Thiel S,, Hartshorn KL . 2012. Human H-ficolin inhibits replication of seasonal and pandemic influenza A viruses. J Immunol 189 : 2478 2487.
51. Garlanda C,, Bottazzi B,, Bastone A,, Mantovani A . 2005. Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Annu Rev Immunol 23 : 337 366.
52. Lu J,, Marnell LL,, Marjon KD,, Mold C,, Du Clos TW,, Sun PD . 2008. Structural recognition and functional activation of FcγR by innate pentraxins. Nature 456 : 989 992.
53. Szalai AJ . 2002. The antimicrobial activity of C-reactive protein. Microbes Infect 4 : 201 205.
54. Noursadeghi M,, Bickerstaff MC,, Gallimore JR,, Herbert J,, Cohen J,, Pepys MB . 2000. Role of serum amyloid P component in bacterial infection: protection of the host or protection of the pathogen. Proc Natl Acad Sci U S A 97 : 14584 14589.
55. Jaillon S,, Bonavita E,, Gentile S,, Rubino M,, Laface I,, Garlanda C,, Mantovani A . 2014. The long pentraxin PTX3 as a key component of humoral innate immunity and a candidate diagnostic for inflammatory diseases. Int Arch Allergy Immunol 165 : 165 178.
56. Nauta AJ,, Daha MR,, van Kooten C,, Roos A . 2003. Recognition and clearance of apoptotic cells: a role for complement and pentraxins. Trends Immunol 24 : 148 154.
57. Gershov D,, Kim S,, Brot N,, Elkon KB . 2000. C-reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: implications for systemic autoimmunity. J Exp Med 192 : 1353 1364.
58. Breviario F,, d’Aniello EM,, Golay J,, Peri G,, Bottazzi B,, Bairoch A,, Saccone S,, Marzella R,, Predazzi V,, Rocchi M,, Della Valle G,, Dejana E,, Mantovani A,, Introna M . 1992. Interleukin-1-inducible genes in endothelial cells. Cloning of a new gene related to C-reactive protein and serum amyloid P component. J Biol Chem 267 : 22190 22197.
59. Lee GW,, Lee TH,, Vilcek J . 1993. TSG-14, a tumor necrosis factor- and IL-1-inducible protein, is a novel member of the pentaxin family of acute phase proteins. J Immunol 150 : 1804 1812.
60. Martinez de la Torre Y,, Fabbri M,, Jaillon S,, Bastone A,, Nebuloni M,, Vecchi A,, Mantovani A,, Garlanda C . 2010. Evolution of the pentraxin family: the new entry PTX4. J Immunol 184 : 5055 5064.
61. Jaillon S,, Moalli F,, Ragnarsdottir B,, Bonavita E,, Puthia M,, Riva F,, Barbati E,, Nebuloni M,, Cvetko Krajinovic L,, Markotic A,, Valentino S,, Doni A,, Tartari S,, Graziani G,, Montanelli A,, Delneste Y,, Svanborg C,, Garlanda C,, Mantovani A . 2014. The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection. Immunity 40 : 621 632.
62. Salio M,, Chimenti S,, De Angelis N,, Molla F,, Maina V,, Nebuloni M,, Pasqualini F,, Latini R,, Garlanda C,, Mantovani A . 2008. Cardioprotective function of the long pentraxin PTX3 in acute myocardial infarction. Circulation 117 : 1055 1064.
63. Bonavita E,, Gentile S,, Rubino M,, Maina V,, Papait R,, Kunderfranco P,, Greco C,, Feruglio F,, Molgora M,, Laface I,, Tartari S,, Doni A,, Pasqualini F,, Barbati E,, Basso G,, Galdiero MR,, Nebuloni M,, Roncalli M,, Colombo P,, Laghi L,, Lambris JD,, Jaillon S,, Garlanda C,, Mantovani A . 2015. PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer. Cell 160 : 700 714.
64. Doni A,, Musso T,, Morone D,, Bastone A,, Zambelli V,, Sironi M,, Castagnoli C,, Cambieri I,, Stravalaci M,, Pasqualini F,, Laface I,, Valentino S,, Tartari S,, Ponzetta A,, Maina V,, Barbieri SS,, Tremoli E,, Catapano AL,, Norata GD,, Bottazzi B,, Garlanda C,, Mantovani A . 2015. An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode. J Exp Med 212 : 905 925.
65. Inforzato A,, Rivieccio V,, Morreale AP,, Bastone A,, Salustri A,, Scarchilli L,, Verdoliva A,, Vincenti S,, Gallo G,, Chiapparino C,, Pacello L,, Nucera E,, Serlupi-Crescenzi O,, Day AJ,, Bottazzi B,, Mantovani A,, De Santis R,, Salvatori G . 2008. Structural characterization of PTX3 disulfide bond network and its multimeric status in cumulus matrix organization. J Biol Chem 283 : 10147 10161.
66. Deban L,, Russo RC,, Sironi M,, Moalli F,, Scanziani M,, Zambelli V,, Cuccovillo I,, Bastone A,, Gobbi M,, Valentino S,, Doni A,, Garlanda C,, Danese S,, Salvatori G,, Sassano M,, Evangelista V,, Rossi B,, Zenaro E,, Constantin G,, Laudanna C,, Bottazzi B,, Mantovani A . 2010. Regulation of leukocyte recruitment by the long pentraxin PTX3. Nat Immunol 11 : 328 334.
67. Jaillon S,, Peri G,, Delneste Y,, Frémaux I,, Doni A,, Moalli F,, Garlanda C,, Romani L,, Gascan H,, Bellocchio S,, Bozza S,, Cassatella MA,, Jeannin P,, Mantovani A . 2007. The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps. J Exp Med 204 : 793 804.
68. Moalli F,, Doni A,, Deban L,, Zelante T,, Zagarella S,, Bottazzi B,, Romani L,, Mantovani A,, Garlanda C . 2010. Role of complement and Fcγ receptors in the protective activity of the long pentraxin PTX3 against Aspergillus fumigatus . Blood 116 : 5170 5180.
69. Garlanda C,, Hirsch E,, Bozza S,, Salustri A,, De Acetis M,, Nota R,, Maccagno A,, Riva F,, Bottazzi B,, Peri G,, Doni A,, Vago L,, Botto M,, De Santis R,, Carminati P,, Siracusa G,, Altruda F,, Vecchi A,, Romani L,, Mantovani A . 2002. Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature 420 : 182 186.
70. Han B,, Haitsma JJ,, Zhang Y,, Bai X,, Rubacha M,, Keshavjee S,, Zhang H,, Liu M . 2011. Long pentraxin PTX3 deficiency worsens LPS-induced acute lung injury. Intensive Care Med 37 : 334 342.
71. Lech M,, Römmele C,, Gröbmayr R,, Eka Susanti H,, Kulkarni OP,, Wang S,, Gröne HJ,, Uhl B,, Reichel C,, Krombach F,, Garlanda C,, Mantovani A,, Anders HJ . 2013. Endogenous and exogenous pentraxin-3 limits postischemic acute and chronic kidney injury. Kidney Int 83 : 647 661.
72. Jeannin P,, Bottazzi B,, Sironi M,, Doni A,, Rusnati M,, Presta M,, Maina V,, Magistrelli G,, Haeuw JF,, Hoeffel G,, Thieblemont N,, Corvaia N,, Garlanda C,, Delneste Y,, Mantovani A . 2005. Complexity and complementarity of outer membrane protein A recognition by cellular and humoral innate immunity receptors. Immunity 22 : 551 560.
73. Cotena A,, Maina V,, Sironi M,, Bottazzi B,, Jeannin P,, Vecchi A,, Corvaia N,, Daha MR,, Mantovani A,, Garlanda C . 2007. Complement dependent amplification of the innate response to a cognate microbial ligand by the long pentraxin PTX3. J Immunol 179 : 6311 6317.
74. Soares AC,, Souza DG,, Pinho V,, Vieira AT,, Nicoli JR,, Cunha FQ,, Mantovani A,, Reis LF,, Dias AA,, Teixeira MM . 2006. Dual function of the long pentraxin PTX3 in resistance against pulmonary infection with Klebsiella pneumoniae in transgenic mice. Microbes Infect 8 : 1321 1329.
75. Ma YJ,, Doni A,, Hummelshøj T,, Honoré C,, Bastone A,, Mantovani A,, Thielens NM,, Garred P . 2009. Synergy between ficolin-2 and pentraxin 3 boosts innate immune recognition and complement deposition. J Biol Chem 284 : 28263 28275.
76. Ma YJ,, Doni A,, Skjoedt MO,, Honoré C,, Arendrup M,, Mantovani A,, Garred P . 2011. Heterocomplexes of mannose-binding lectin and the pentraxins PTX3 or serum amyloid P component trigger cross-activation of the complement system. J Biol Chem 286 : 3405 3417.
77. Ma YJ,, Doni A,, Romani L,, Jürgensen HJ,, Behrendt N,, Mantovani A,, Garred P . 2013. Ficolin-1-PTX3 complex formation promotes clearance of altered self-cells and modulates IL-8 production. J Immunol 191 : 1324 1333.
78. Braunschweig A,, Józsi M . 2011. Human pentraxin 3 binds to the complement regulator c4b-binding protein. PLoS One 6 : e23991. doi:10.1371/journal.pone.0023991.
79. Deban L,, Jarva H,, Lehtinen MJ,, Bottazzi B,, Bastone A,, Doni A,, Jokiranta TS,, Mantovani A,, Meri S . 2008. Binding of the long pentraxin PTX3 to factor H: interacting domains and function in the regulation of complement activation. J Immunol 181 : 8433 8440.
80. Csincsi AI,, Kopp A,, Zöldi M,, Bánlaki Z,, Uzonyi B,, Hebecker M,, Caesar JJ,, Pickering MC,, Daigo K,, Hamakubo T,, Lea SM,, Goicoechea de Jorge E,, Józsi M . 2015. Factor H-related protein 5 interacts with pentraxin 3 and the extracellular matrix and modulates complement activation. J Immunol 194 : 4963 4973.
81. Dziarski R,, Gupta D . 2006. Mammalian PGRPs: novel antibacterial proteins. Cell Microbiol 8 : 1059 1069.
82. Kietzman C,, Tuomanen E . 2011. PGRPs kill with an ancient weapon. Nat Med 17 : 665 666.
83. Dziarski R,, Gupta D . 2010. Review: mammalian peptidoglycan recognition proteins (PGRPs) in innate immunity. Innate Immun 16 : 168 174.
84. Kashyap DR,, Wang M,, Liu LH,, Boons GJ,, Gupta D,, Dziarski R . 2011. Peptidoglycan recognition proteins kill bacteria by activating protein-sensing two-component systems. Nat Med 17 : 676 683.
85. O’Brien KD,, Chait A . 2006. Serum amyloid A: the “other” inflammatory protein. Curr Atheroscler Rep 8 : 62 68.
86. Shah C,, Hari-Dass R,, Raynes JG . 2006. Serum amyloid A is an innate immune opsonin for Gram-negative bacteria. Blood 108 : 1751 1757.
87. Cai Z,, Cai L,, Jiang J,, Chang KS,, van der Westhuyzen DR,, Luo G . 2007. Human serum amyloid A protein inhibits hepatitis C virus entry into cells. J Virol 81 : 6128 6133.
88. Deguchi A,, Tomita T,, Omori T,, Komatsu A,, Ohto U,, Takahashi S,, Tanimura N,, Akashi-Takamura S,, Miyake K,, Maru Y . 2013. Serum amyloid A3 binds MD-2 to activate p38 and NF-κB pathways in a MyD88-dependent manner. J Immunol 191 : 1856 1864.
89. Ather JL,, Ckless K,, Martin R,, Foley KL,, Suratt BT,, Boyson JE,, Fitzgerald KA,, Flavell RA,, Eisenbarth SC,, Poynter ME . 2011. Serum amyloid A activates the NLRP3 inflammasome and promotes Th17 allergic asthma in mice. J Immunol 187 : 64 73.
90. Sun L,, Zhu Z,, Cheng N,, Yan Q,, Ye RD . 2014. Serum amyloid A induces interleukin-33 expression through an IRF7-dependent pathway. Eur J Immunol 44 : 2153 2164.
91. Bowdish DM,, Loffredo MS,, Mukhopadhyay S,, Mantovani A,, Gordon S . 2007. Macrophage receptors implicated in the “adaptive” form of innate immunity. Microbes Infect 9 : 1680 1687.
92. Takeuchi O,, Akira S . 2010. Pattern recognition receptors and inflammation. Cell 140 : 805 820.
93. Jeannin P,, Jaillon S,, Delneste Y . 2008. Pattern recognition receptors in the immune response against dying cells. Curr Opin Immunol 20 : 530 537.
94. Diniz SN,, Nomizo R,, Cisalpino PS,, Teixeira MM,, Brown GD,, Mantovani A,, Gordon S,, Reis LF,, Dias AA . 2004. PTX3 function as an opsonin for the dectin-1-dependent internalization of zymosan by macrophages. J Leukoc Biol 75 : 649 656.
95. Frankenberger M,, Schwaeble W,, Ziegler-Heitbrock L . 2008. Expression of M-Ficolin in human monocytes and macrophages. Mol Immunol 45 : 1424 1430.
96. Jaillon S,, Galdiero MR,, Del Prete D,, Cassatella MA,, Garlanda C,, Mantovani A . 2013. Neutrophils in innate and adaptive immunity. Semin Immunopathol 35 : 377 394.
97. Greenblatt MB,, Aliprantis A,, Hu B,, Glimcher LH . 2010. Calcineurin regulates innate antifungal immunity in neutrophils. J Exp Med 207 : 923 931.
98. Li D,, Dong B,, Tong Z,, Wang Q,, Liu W,, Wang Y,, Liu W,, Chen J,, Xu L,, Chen L,, Duan Y . 2012. MBL-mediated opsonophagocytosis of Candida albicans by human neutrophils is coupled with intracellular Dectin-1-triggered ROS production. PLoS One 7 : e50589. doi:10.1371/journal.pone.0050589.
99. Liu X,, Ma B,, Malik AB,, Tang H,, Yang T,, Sun B,, Wang G,, Minshall RD,, Li Y,, Zhao Y,, Ye RD,, Xu J . 2012. Bidirectional regulation of neutrophil migration by mitogen-activated protein kinases. Nat Immunol 13 : 457 464.
100. McDonald B,, Pittman K,, Menezes GB,, Hirota SA,, Slaba I,, Waterhouse CC,, Beck PL,, Muruve DA,, Kubes P . 2010. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science 330 : 362 366.
101. Tamassia N,, Bazzoni F,, Le Moigne V,, Calzetti F,, Masala C,, Grisendi G,, Bussmeyer U,, Scutera S,, De Gironcoli M,, Costantini C,, Musso T,, Cassatella MA . 2012. IFN-β expression is directly activated in human neutrophils transfected with plasmid DNA and is further increased via TLR-4-mediated signaling. J Immunol 189 : 1500 1509.
102. Brinkmann V,, Reichard U,, Goosmann C,, Fauler B,, Uhlemann Y,, Weiss DS,, Weinrauch Y,, Zychlinsky A . 2004. Neutrophil extracellular traps kill bacteria. Science 303 : 1532 1535.
103. Saitoh T,, Komano J,, Saitoh Y,, Misawa T,, Takahama M,, Kozaki T,, Uehata T,, Iwasaki H,, Omori H,, Yamaoka S,, Yamamoto N,, Akira S . 2012. Neutrophil extracellular traps mediate a host defense response to human immunodeficiency virus-1. Cell Host Microbe 12 : 109 116.
104. Jenne CN,, Wong CH,, Zemp FJ,, McDonald B,, Rahman MM,, Forsyth PA,, McFadden G,, Kubes P . 2013. Neutrophils recruited to sites of infection protect from virus challenge by releasing neutrophil extracellular traps. Cell Host Microbe 13 : 169 180.
105. Douda DN,, Jackson R,, Grasemann H,, Palaniyar N . 2011. Innate immune collectin surfactant protein D simultaneously binds both neutrophil extracellular traps and carbohydrate ligands and promotes bacterial trapping. J Immunol 187 : 1856 1865.
106. Jaillon S,, Jeannin P,, Hamon Y,, Frémaux I,, Doni A,, Bottazzi B,, Blanchard S,, Subra JF,, Chevailler A,, Mantovani A,, Delneste Y . 2009. Endogenous PTX3 translocates at the membrane of late apoptotic human neutrophils and is involved in their engulfment by macrophages. Cell Death Differ 16 : 465 474.
107. Cho JH,, Fraser IP,, Fukase K,, Kusumoto S,, Fujimoto Y,, Stahl GL,, Ezekowitz RA . 2005. Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity. Blood 106 : 2551 2558.
108. Rørvig S,, Honore C,, Larsson LI,, Ohlsson S,, Pedersen CC,, Jacobsen LC,, Cowland JB,, Garred P,, Borregaard N . 2009. Ficolin-1 is present in a highly mobilizable subset of human neutrophil granules and associates with the cell surface after stimulation with fMLP. J Leukoc Biol 86 : 1439 1449.
109. Dziarski R,, Platt KA,, Gelius E,, Steiner H,, Gupta D . 2003. Defect in neutrophil killing and increased susceptibility to infection with nonpathogenic gram-positive bacteria in peptidoglycan recognition protein-S (PGRP-S)-deficient mice. Blood 102 : 689 697.
110. Moreno-Amaral AN,, Gout E,, Danella-Polli C,, Tabarin F,, Lesavre P,, Pereira-da-Silva G,, Thielens NM,, Halbwachs-Mecarelli L . 2012. M-Ficolin and leukosialin (CD43): new partners in neutrophil adhesion. J Leukoc Biol 91 : 469 474.
111. Han B,, Ma X,, Zhang J,, Zhang Y,, Bai X,, Hwang DM,, Keshavjee S,, Levy GA,, McGilvray I,, Liu M . 2012. Protective effects of long pentraxin PTX3 on lung injury in a severe acute respiratory syndrome model in mice. Lab Invest 92 : 1285 1296.
112. Bozza S,, Bistoni F,, Gaziano R,, Pitzurra L,, Zelante T,, Bonifazi P,, Perruccio K,, Bellocchio S,, Neri M,, Iorio AM,, Salvatori G,, De Santis R,, Calvitti M,, Doni A,, Garlanda C,, Mantovani A,, Romani L . 2006. Pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation. Blood 108 : 3387 3396.
113. Reading PC,, Bozza S,, Gilbertson B,, Tate M,, Moretti S,, Job ER,, Crouch EC,, Brooks AG,, Brown LE,, Bottazzi B,, Romani L,, Mantovani A . 2008. Antiviral activity of the long chain pentraxin PTX3 against influenza viruses. J Immunol 180 : 3391 3398.
114. Job ER,, Bottazzi B,, Short KR,, Deng YM,, Mantovani A,, Brooks AG,, Reading PC . 2014. A single amino acid substitution in the hemagglutinin of H3N2 subtype influenza A viruses is associated with resistance to the long pentraxin PTX3 and enhanced virulence in mice. J Immunol 192 : 271 281.
115. Job ER,, Deng YM,, Tate MD,, Bottazzi B,, Crouch EC,, Dean MM,, Mantovani A,, Brooks AG,, Reading PC . 2010. Pandemic H1N1 influenza A viruses are resistant to the antiviral activities of innate immune proteins of the collectin and pentraxin superfamilies. J Immunol 185 : 4284 4291.
116. Bozza S,, Campo S,, Arseni B,, Inforzato A,, Ragnar L,, Bottazzi B,, Mantovani A,, Moretti S,, Oikonomous V,, De Santis R,, Carvalho A,, Salvatori G,, Romani L . 2014. PTX3 binds MD-2 and promotes TRIF-dependent immune protection in aspergillosis. J Immunol 193 : 2340 2348.
117. Davey MS,, Tamassia N,, Rossato M,, Bazzoni F,, Calzetti F,, Bruderek K,, Sironi M,, Zimmer L,, Bottazzi B,, Mantovani A,, Brandau S,, Moser B,, Eberl M,, Cassatella MA . 2011. Failure to detect production of IL-10 by activated human neutrophils. Nat Immunol 12 : 1017 1018, author reply 1018–1020.
118. Barbati E,, Specchia C,, Villella M,, Rossi ML,, Barlera S,, Bottazzi B,, Crociati L,, d’Arienzo C,, Fanelli R,, Garlanda C,, Gori F,, Mango R,, Mantovani A,, Merla G,, Nicolis EB,, Pietri S,, Presbitero P,, Sudo Y,, Villella A,, Franzosi MG . 2012. Influence of pentraxin 3 (PTX3) genetic variants on myocardial infarction risk and PTX3 plasma levels. PLoS One 7 : e53030. doi:10.1371/journal.pone.0053030.
119. Cunha C,, Aversa F,, Lacerda JF,, Busca A,, Kurzai O,, Grube M,, Löffler J,, Maertens JA,, Bell AS,, Inforzato A,, Barbati E,, Almeida B,, Santos e Sousa P,, Barbui A,, Potenza L,, Caira M,, Rodrigues F,, Salvatori G,, Pagano L,, Luppi M,, Mantovani A,, Velardi A,, Romani L,, Carvalho A . 2014. Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation. N Engl J Med 370 : 421 432.
120. Bottazzi B,, Santini L,, Savino S,, Giuliani MM,, Dueñas Díez AI,, Mancuso G,, Beninati C,, Sironi M,, Valentino S,, Deban L,, Garlanda C,, Teti G,, Pizza M,, Rappuoli R,, Mantovani A . 2015. Recognition of Neisseria meningitidis by the long pentraxin PTX3 and its role as an endogenous adjuvant. PLoS One 10 : e0120807. doi:10.1371/journal.pone.0120807.
121. Moalli F,, Paroni M,, Véliz Rodriguez T,, Riva F,, Polentarutti N,, Bottazzi B,, Valentino S,, Mantero S,, Nebuloni M,, Mantovani A,, Bragonzi A,, Garlanda C . 2011. The therapeutic potential of the humoral pattern recognition molecule PTX3 in chronic lung infection caused by Pseudomonas aeruginosa . J Immunol 186 : 5425 5434.
122. Jaillon S,, Mancuso G,, Hamon Y,, Beauvillain C,, Cotici V,, Midiri A,, Bottazzi B,, Nebuloni M,, Garlanda C,, Frémaux I,, Gauchat JF,, Descamps P,, Beninati C,, Mantovani A,, Jeannin P,, Delneste Y . 2013. Prototypic long pentraxin PTX3 is present in breast milk, spreads in tissues, and protects neonate mice from Pseudomonas aeruginosa lung infection. J Immunol 191 : 1873 1882.
123. Chiarini M,, Sabelli C,, Melotti P,, Garlanda C,, Savoldi G,, Mazza C,, Padoan R,, Plebani A,, Mantovani A,, Notarangelo LD,, Assael BM,, Badolato R . 2010. PTX3 genetic variations affect the risk of Pseudomonas aeruginosa airway colonization in cystic fibrosis patients. Genes Immun 11 : 665 670.
124. Olesen R,, Wejse C,, Velez DR,, Bisseye C,, Sodemann M,, Aaby P,, Rabna P,, Worwui A,, Chapman H,, Diatta M,, Adegbola RA,, Hill PC,, Østergaard L,, Williams SM,, Sirugo G . 2007. DC-SIGN (CD209), pentraxin 3 and vitamin D receptor gene variants associate with pulmonary tuberculosis risk in West Africans. Genes Immun 8 : 456 467.
125. Baruah P,, Dumitriu IE,, Peri G,, Russo V,, Mantovani A,, Manfredi AA,, Rovere-Querini P . 2006. The tissue pentraxin PTX3 limits C1q-mediated complement activation and phagocytosis of apoptotic cells by dendritic cells. J Leukoc Biol 80 : 87 95.
126. Nauta AJ,, Bottazzi B,, Mantovani A,, Salvatori G,, Kishore U,, Schwaeble WJ,, Gingras AR,, Tzima S,, Vivanco F,, Egido J,, Tijsma O,, Hack EC,, Daha MR,, Roos A . 2003. Biochemical and functional characterization of the interaction between pentraxin 3 and C1q. Eur J Immunol 33 : 465 473.
127. Guo T,, Ke L,, Qi B,, Wan J,, Ge J,, Bai L,, Cheng B . 2012. PTX3 is located at the membrane of late apoptotic macrophages and mediates the phagocytosis of macrophages. J Clin Immunol 32 : 330 339.
128. Ley K,, Reutershan J . 2006. Leucocyte-endothelial interactions in health and disease. Handbook Exp Pharmacol 2006 : 97 133.


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Table 1

Expression sites, ligands, and activities of soluble PRMs

Citation: Jaillon S, Bonavita E, Garlanda C, Mantovani A. 2017. Interplay between Myeloid Cells and Humoral Innate Immunity, p 661-678. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0051-2016

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