Immune Antibodies and Helminth Products Drive CXCR2-Dependent Macrophage-Myofibroblast Crosstalk to Promote Intestinal Repair
To complete their lifecycles, helminth parasites have to migrate through tissues such as the skin, lung, liver and intestine. This migration causes severe tissue damage, resulting in the need for rapid repair to restore the integrity and function of damaged tissues. Protective type 2 immune responses against helminths can repair acute lung damage, but they can also promote liver fibrosis. However, how protective immune mechanisms might contribute to wound healing during enteric nematode infection has remained unclear. Here we show that during a protective antibody response, where helminth larvae are trapped in the intestinal mucosa, macrophages and myofibroblasts secrete chemokines, which promote the repair of helminth-caused lesions. Chemokine secretion by macrophages was triggered by antibodies and helminth products, whilst myofibroblasts produced chemokines directly in response to innate recognition of helminth products. The same chemokines that instructed intestinal repair in mice were also secreted by human macrophages, when co-cultured with immune serum and helminths. Finally, human myofibroblasts closed in vitro scratch wounds more rapidly, when stimulated with the chemokine secretions of helminth-antibody activated human macrophages. Thus, our findings reveal a novel mechanism, by which a protective antibody response can promote the repair of intestinal injury during helminth infection.
Vyšlo v časopise:
Immune Antibodies and Helminth Products Drive CXCR2-Dependent Macrophage-Myofibroblast Crosstalk to Promote Intestinal Repair. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004778
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004778
Souhrn
To complete their lifecycles, helminth parasites have to migrate through tissues such as the skin, lung, liver and intestine. This migration causes severe tissue damage, resulting in the need for rapid repair to restore the integrity and function of damaged tissues. Protective type 2 immune responses against helminths can repair acute lung damage, but they can also promote liver fibrosis. However, how protective immune mechanisms might contribute to wound healing during enteric nematode infection has remained unclear. Here we show that during a protective antibody response, where helminth larvae are trapped in the intestinal mucosa, macrophages and myofibroblasts secrete chemokines, which promote the repair of helminth-caused lesions. Chemokine secretion by macrophages was triggered by antibodies and helminth products, whilst myofibroblasts produced chemokines directly in response to innate recognition of helminth products. The same chemokines that instructed intestinal repair in mice were also secreted by human macrophages, when co-cultured with immune serum and helminths. Finally, human myofibroblasts closed in vitro scratch wounds more rapidly, when stimulated with the chemokine secretions of helminth-antibody activated human macrophages. Thus, our findings reveal a novel mechanism, by which a protective antibody response can promote the repair of intestinal injury during helminth infection.
Zdroje
1. Bethony J, Brooker S, Albonico M, Geiger SM, Loukas A, Diemert D, et al. Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm. Lancet. 2006;367: 1521–1532. 16679166
2. Yang G-J, Liu L, Zhu H-R, Griffiths SM, Tanner M, Bergquist R, et al. China’s sustained drive to eliminate neglected tropical diseases. Lancet Infect Dis. 2014;
3. Geerts S, Gryseels B. Drug resistance in human helminths: current situation and lessons from livestock. Clin Microbiol Rev. 2000;13: 207–222. 10755998
4. Rinaldi M, Geldhof P. Immunologically based control strategies for ostertagiosis in cattle: where do we stand? Parasite Immunol. 2012;34: 254–264. doi: 10.1111/j.1365-3024.2011.01313.x 21722144
5. Salgame P, Yap GS, Gause WC. Effect of helminth-induced immunity on infections with microbial pathogens. Nat Immunol. 2013;14: 1118–1126. doi: 10.1038/ni.2736 24145791
6. Urban JF Jr, Steenhard NR, Solano-Aguilar GI, Dawson HD, Iweala OI, Nagler CR, et al. Infection with parasitic nematodes confounds vaccination efficacy. Vet Parasitol. 2007;148: 14–20. 17587500
7. Allen JE, Maizels RM. Diversity and dialogue in immunity to helminths. Nat Rev Immunol. 2011;11: 375–388. doi: 10.1038/nri2992 21610741
8. Allen JE, Sutherland TE. Host protective roles of type 2 immunity: Parasite killing and tissue repair, flip sides of the same coin. Semin Immunol. 2014;
9. Chen F, Liu Z, Wu W, Rozo C, Bowdridge S, Millman A, et al. An essential role for T(H)2-type responses in limiting acute tissue damage during experimental helminth infection. Nat Med. 2012;
10. Esser-von Bieren J, Mosconi I, Guiet R, Piersgilli A, Volpe B, Chen F, et al. Antibodies Trap Tissue Migrating Helminth Larvae and Prevent Tissue Damage by Driving IL-4Rα-Independent Alternative Differentiation of Macrophages. PLoS Pathog. 2013;9: e1003771. doi: 10.1371/journal.ppat.1003771 24244174
11. Hübner MP, Layland LE, Hoerauf A. Helminths and their implication in sepsis—a new branch of their immunomodulatory behaviour? Pathog Dis. 2013;69: 127–141. doi: 10.1111/2049-632X.12080 23929557
12. Gause WC, Wynn TA, Allen JE. Type 2 immunity and wound healing: evolutionary refinement of adaptive immunity by helminths. Nat Rev Immunol. 2013;
13. Massacand JC, Stettler RC, Meier R, Humphreys NE, Grencis RK, Marsland BJ, et al. Helminth products bypass the need for TSLP in Th2 immune responses by directly modulating dendritic cell function. Proc Natl Acad Sci U S A. 2009;106: 13968–13973. doi: 10.1073/pnas.0906367106 19666528
14. Patel N, Wu W, Mishra PK, Chen F, Millman A, Csóka B, et al. A2B adenosine receptor induces protective antihelminth type 2 immune responses. Cell Host Microbe. 2014;15: 339–350. doi: 10.1016/j.chom.2014.02.001 24629340
15. Saenz SA, Taylor BC, Artis D. Welcome to the neighborhood: epithelial cell-derived cytokines license innate and adaptive immune responses at mucosal sites. Immunol Rev. 2008;226: 172–190. doi: 10.1111/j.1600-065X.2008.00713.x 19161424
16. Pesce JT, Ramalingam TR, Mentink-Kane MM, Wilson MS, El Kasmi KC, Smith AM, et al. Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis. PLoS Pathog. 2009;5: e1000371. doi: 10.1371/journal.ppat.1000371 19360123
17. Turner J-E, Morrison PJ, Wilhelm C, Wilson M, Ahlfors H, Renauld J-C, et al. IL-9-mediated survival of type 2 innate lymphoid cells promotes damage control in helminth-induced lung inflammation. J Exp Med. 2013;210: 2951–2965. doi: 10.1084/jem.20130071 24249111
18. Maizels RM, Hewitson JP, Gause WC. Heligmosomoides polygyrus: one species still. Trends Parasitol. 2011;27: 100–101. doi: 10.1016/j.pt.2010.11.004 21159557
19. McCoy KD, Stoel M, Stettler R, Merky P, Fink K, Senn BM, et al. Polyclonal and specific antibodies mediate protective immunity against enteric helminth infection. Cell Host Microbe. 2008;4: 362–373. doi: 10.1016/j.chom.2008.08.014 18854240
20. Esser-von Bieren J, Volpe B, Kulagin M, Sutherland DB, Guiet R, Seitz A, et al. Antibody-Mediated Trapping of Helminth Larvae Requires CD11b and Fcγ Receptor I. J Immunol. 2015;194: 1154–1163. doi: 10.4049/jimmunol.1401645 25548226
21. Devalaraja RM, Nanney LB, Du J, Qian Q, Yu Y, Devalaraja MN, et al. Delayed wound healing in CXCR2 knockout mice. J Invest Dermatol. 2000;115: 234–244. 10951241
22. Milatovic S, Nanney LB, Yu Y, White JR, Richmond A. Impaired healing of nitrogen mustard wounds in CXCR2 null mice. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc. 2003;11: 213–219.
23. Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol. 2011;11: 723–737. doi: 10.1038/nri3073 21997792
24. Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell. 2000;102: 553–563. 11007474
25. Herbst T, Esser J, Prati M, Kulagin M, Stettler R, Zaiss MM, et al. Antibodies and IL-3 support helminth-induced basophil expansion. Proc Natl Acad Sci U S A. 2012;109: 14954–14959. doi: 10.1073/pnas.1117584109 22930820
26. Hinz B. The myofibroblast: paradigm for a mechanically active cell. J Biomech. 2010;43: 146–155. doi: 10.1016/j.jbiomech.2009.09.020 19800625
27. Su F, Huang H, Akieda K, Occhipinti G, Donadello K, Piagnerelli M, et al. Effects of a selective iNOS inhibitor versus norepinephrine in the treatment of septic shock. Shock Augusta Ga. 2010;34: 243–249. doi: 10.1097/SHK.0b013e3181d75967 20160666
28. Al-Alwan LA, Chang Y, Mogas A, Halayko AJ, Baglole CJ, Martin JG, et al. Differential Roles of CXCL2 and CXCL3 and Their Receptors in Regulating Normal and Asthmatic Airway Smooth Muscle Cell Migration. J Immunol Baltim Md 1950. 2013;191: 2731–2741. doi: 10.4049/jimmunol.1203421 23904157
29. Perl A-KT, Gale E. FGF signaling is required for myofibroblast differentiation during alveolar regeneration. Am J Physiol Lung Cell Mol Physiol. 2009;297: L299–308. doi: 10.1152/ajplung.00008.2009 19502291
30. Barron L, Wynn TA. Fibrosis is regulated by Th2 and Th17 responses and by dynamic interactions between fibroblasts and macrophages. Am J Physiol Gastrointest Liver Physiol. 2011;300: G723–728. doi: 10.1152/ajpgi.00414.2010 21292997
31. Anthony RM, Urban JF Jr, Alem F, Hamed HA, Rozo CT, Boucher J-L, et al. Memory T(H)2 cells induce alternatively activated macrophages to mediate protection against nematode parasites. Nat Med. 2006;12: 955–960. 16892038
32. Shibata F, Konishi K, Nakagawa H. Chemokine receptor CXCR2 activates distinct pathways for chemotaxis and calcium mobilization. Biol Pharm Bull. 2002;25: 1217–1219. 12230122
33. Driscoll KE, Hassenbein DG, Carter J, Poynter J, Asquith TN, Grant RA, et al. Macrophage inflammatory proteins 1 and 2: expression by rat alveolar macrophages, fibroblasts, and epithelial cells and in rat lung after mineral dust exposure. Am J Respir Cell Mol Biol. 1993;8: 311–318. 8383510
34. Van Liempt E, van Vliet SJ, Engering A, García Vallejo JJ, Bank CMC, Sanchez-Hernandez M, et al. Schistosoma mansoni soluble egg antigens are internalized by human dendritic cells through multiple C-type lectins and suppress TLR-induced dendritic cell activation. Mol Immunol. 2007;44: 2605–2615. 17241663
35. Ritter M, Gross O, Kays S, Ruland J, Nimmerjahn F, Saijo S, et al. Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses. Proc Natl Acad Sci U S A. 2010;107: 20459–20464. doi: 10.1073/pnas.1010337107 21059925
36. Sato K, Yang X, Yudate T, Chung J-S, Wu J, Luby-Phelps K, et al. Dectin-2 is a pattern recognition receptor for fungi that couples with the Fc receptor gamma chain to induce innate immune responses. J Biol Chem. 2006;281: 38854–38866. 17050534
37. Graham LM, Brown GD. The Dectin-2 family of C-type lectins in immunity and homeostasis. Cytokine. 2009;48: 148–155. doi: 10.1016/j.cyto.2009.07.010 19665392
38. Galioto AM, Hess JA, Nolan TJ, Schad GA, Lee JJ, Abraham D. Role of eosinophils and neutrophils in innate and adaptive protective immunity to larval strongyloides stercoralis in mice. Infect Immun. 2006;74: 5730–5738. 16988250
39. Hall LR, Diaconu E, Patel R, Pearlman E. CXC chemokine receptor 2 but not C-C chemokine receptor 1 expression is essential for neutrophil recruitment to the cornea in helminth-mediated keratitis (river blindness). J Immunol Baltim Md 1950. 2001;166: 4035–4041. 11238651
40. Sutherland TE, Logan N, Rückerl D, Humbles AA, Allan SM, Papayannopoulos V, et al. Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage. Nat Immunol. 2014;15: 1116–1125. doi: 10.1038/ni.3023 25326751
41. Zhou C, Li M, Yuan K, Deng S, Peng W. Pig Ascaris: An important source of human ascariasis in China. Infect Genet Evol J Mol Epidemiol Evol Genet Infect Dis. 2012;12: 1172–1177
42. Laubach HE. Cytoadherence effects of serum on Ascaris suum infective larvae. Zentralblatt Für Bakteriol Mikrobiol Hyg 1 Abt Orig Med Mikrobiol Infekt Parasitol Int J Microbiol Hyg Med Microbiol Infect Parasitol. 1983;255: 406–412.
43. Gao Y, Flori L, Lecardonnel J, Esquerré D, Hu Z-L, Teillaud A, et al. Transcriptome analysis of porcine PBMCs after in vitro stimulation by LPS or PMA/ionomycin using an expression array targeting the pig immune response. BMC Genomics. 2010;11: 292. doi: 10.1186/1471-2164-11-292 20459780
44. Tekamp-Olson P, Gallegos C, Bauer D, McClain J, Sherry B, Fabre M, et al. Cloning and characterization of cDNAs for murine macrophage inflammatory protein 2 and its human homologues. J Exp Med. 1990;172: 911–919. 2201751
45. Blackwell NM, Else KJ. B cells and antibodies are required for resistance to the parasitic gastrointestinal nematode Trichuris muris. Infect Immun. 2001;69: 3860–3868. 11349052
46. Gurish MF, Bryce PJ, Tao H, Kisselgof AB, Thornton EM, Miller HR, et al. IgE enhances parasite clearance and regulates mast cell responses in mice infected with Trichinella spiralis. J Immunol Baltim Md 1950. 2004;172: 1139–1145. 14707089
47. Pearlman E, Hall LR, Higgins AW, Bardenstein DS, Diaconu E, Hazlett FE, et al. The role of eosinophils and neutrophils in helminth-induced keratitis. Invest Ophthalmol Vis Sci. 1998;39: 1176–1182. 9620077
48. Chen F, Wu W, Millman A, Craft JF, Chen E, Patel N, et al. Neutrophils prime a long-lived effector macrophage phenotype that mediates accelerated helminth expulsion. Nat Immunol. 2014;
49. Hung L-Y, Lewkowich IP, Dawson LA, Downey J, Yang Y, Smith DE, et al. IL-33 drives biphasic IL-13 production for noncanonical Type 2 immunity against hookworms. Proc Natl Acad Sci U S A. 2013;110: 282–287. doi: 10.1073/pnas.1206587110 23248269
50. Owyang AM, Zaph C, Wilson EH, Guild KJ, McClanahan T, Miller HRP, et al. Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract. J Exp Med. 2006;203: 843–849. 16606667
51. Obata-Ninomiya K, Ishiwata K, Tsutsui H, Nei Y, Yoshikawa S, Kawano Y, et al. The skin is an important bulwark of acquired immunity against intestinal helminths. J Exp Med. 2013;210: 2583–2595. doi: 10.1084/jem.20130761 24166714
52. Mizutani N, Nabe T, Yoshino S. IL-17A Promotes the Exacerbation of IL-33-Induced Airway Hyperresponsiveness by Enhancing Neutrophilic Inflammation via CXCR2 Signaling in Mice. J Immunol Baltim Md 1950. 2014;192: 1372–1384. doi: 10.4049/jimmunol.1301538 24446518
53. Harvath L. Neutrophil chemotactic factors. EXS. 1991;59: 35–52. 1655519
54. Davids JS, Carothers AM, Damas BC, Bertagnolli MM. Chronic cyclooxygenase-2 inhibition promotes myofibroblast-associated intestinal fibrosis. Cancer Prev Res Phila Pa. 2010;3: 348–358. doi: 10.1158/1940-6207.CAPR-09-0146 20179298
55. Kabashima K, Saji T, Murata T, Nagamachi M, Matsuoka T, Segi E, et al. The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut. J Clin Invest. 2002;109: 883–893. 11927615
56. Yin H, Li X, Hu S, Liu T, Yuan B, Ni Q, et al. IL-33 promotes Staphylococcus aureus-infected wound healing in mice. Int Immunopharmacol. 2013;17: 432–438. doi: 10.1016/j.intimp.2013.07.008 23892028
57. Schwartz C, Turqueti-Neves A, Hartmann S, Yu P, Nimmerjahn F, Voehringer D. Basophil-mediated protection against gastrointestinal helminths requires IgE-induced cytokine secretion. Proc Natl Acad Sci U S A. 2014;
58. Reutershan J. CXCR2—the receptor to hit? Drug News Perspect. 2006;19: 615–623. doi: 10.1358/dnp.2006.19.10.1068009 17299604
59. Zenobia C, Luo XL, Hashim A, Abe T, Jin L, Chang Y, et al. Commensal bacteria-dependent select expression of CXCL2 contributes to periodontal tissue homeostasis. Cell Microbiol. 2013;15: 1419–1426. doi: 10.1111/cmi.12127 23433011
60. Auten RL, Richardson RM, White JR, Mason SN, Vozzelli MA, Whorton MH. Nonpeptide CXCR2 antagonist prevents neutrophil accumulation in hyperoxia-exposed newborn rats. J Pharmacol Exp Ther. 2001;299: 90–95. 11561067
61. Urban JF Jr, Douvres FW, Tromba FG. A rapid method for hatching Ascaris suum eggs in vitro. Proc Helminthol Soc Wash. 1981;48: 241–243.
62. Esser J, Gehrmann U, D’Alexandri FL, Hidalgo-Estévez AM, Wheelock CE, Scheynius A, et al. Exosomes from human macrophages and dendritic cells contain enzymes for leukotriene biosynthesis and promote granulocyte migration. J Allergy Clin Immunol. 2010;126: 1032–1040, 1040.e1–4. doi: 10.1016/j.jaci.2010.06.039 20728205
63. Kamata T, Nogaki F, Fagarasan S, Sakiyama T, Kobayashi I, Miyawaki S, et al. Increased frequency of surface IgA-positive plasma cells in the intestinal lamina propria and decreased IgA excretion in hyper IgA (HIGA) mice, a murine model of IgA nephropathy with hyperserum IgA. J Immunol Baltim Md 1950. 2000;165: 1387–1394. 10903742
64. Van Tol EA, Holt L, Li FL, Kong FM, Rippe R, Yamauchi M, et al. Bacterial cell wall polymers promote intestinal fibrosis by direct stimulation of myofibroblasts. Am J Physiol. 1999;277: G245–255. 10409173
65. Iwanaga K, Okada M, Murata T, Hori M, Ozaki H. Prostaglandin E2 promotes wound-induced migration of intestinal subepithelial myofibroblasts via EP2, EP3, and EP4 prostanoid receptor activation. J Pharmacol Exp Ther. 2012;340: 604–611. doi: 10.1124/jpet.111.189845 22138372
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2015 Číslo 3
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- Bacterial Immune Evasion through Manipulation of Host Inhibitory Immune Signaling
- Antimicrobial-Induced DNA Damage and Genomic Instability in Microbial Pathogens
- Is Antigenic Sin Always “Original?” Re-examining the Evidence Regarding Circulation of a Human H1 Influenza Virus Immediately Prior to the 1918 Spanish Flu
- An 18 kDa Scaffold Protein Is Critical for Biofilm Formation