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IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Infection


In this study, B cell function in protective TH2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Rα and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific IL-4Rα−/− mice resulted in increased worm burdens compared to control mice, despite their equivalent capacity to control primary infection. Impaired protection correlated with reduced lymphocyte IL-13 production and B cell MHC class II and CD86 surface expression. Adoptive transfer of in vivo N. brasiliensis primed IL-4Rα expressing B cells into naïve BALB/c mice, but not IL-4Rα or IL-13 deficient B cells, conferred protection against primary N. brasiliensis infection. This protection required MHC class II compatibility on B cells suggesting cognate interactions by B cells with CD4+ T cells were important to co-ordinate immunity. Furthermore, the rapid nature of these protective effects by B cells suggested non-BCR mediated mechanisms, such as via Toll Like Receptors, was involved, and this was supported by transfer experiments using antigen pulsed Myd88−/− B cells. These data suggest TLR dependent antigen processing by IL-4Rα-responsive B cells producing IL-13 contribute significantly to CD4+ T cell-mediated protective immunity against N. brasiliensis infection.


Vyšlo v časopise: IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Infection. PLoS Pathog 9(10): e32767. doi:10.1371/journal.ppat.1003662
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003662

Souhrn

In this study, B cell function in protective TH2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Rα and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific IL-4Rα−/− mice resulted in increased worm burdens compared to control mice, despite their equivalent capacity to control primary infection. Impaired protection correlated with reduced lymphocyte IL-13 production and B cell MHC class II and CD86 surface expression. Adoptive transfer of in vivo N. brasiliensis primed IL-4Rα expressing B cells into naïve BALB/c mice, but not IL-4Rα or IL-13 deficient B cells, conferred protection against primary N. brasiliensis infection. This protection required MHC class II compatibility on B cells suggesting cognate interactions by B cells with CD4+ T cells were important to co-ordinate immunity. Furthermore, the rapid nature of these protective effects by B cells suggested non-BCR mediated mechanisms, such as via Toll Like Receptors, was involved, and this was supported by transfer experiments using antigen pulsed Myd88−/− B cells. These data suggest TLR dependent antigen processing by IL-4Rα-responsive B cells producing IL-13 contribute significantly to CD4+ T cell-mediated protective immunity against N. brasiliensis infection.


Zdroje

1. HotezPJ, BrindleyPJ, BethonyJM, KingCH, PearceEJ, et al. (2008) Helminth infections: the great neglected tropical diseases. J Clin Invest 118: 1311–1321.

2. BethonyJ, BrookerS, AlbonicoM, GeigerSM, LoukasA, et al. (2006) Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm. Lancet 367: 1521–1532.

3. HotezPJ (2007) Hookworm and Poverty. Ann N Y Acad Sci 1136: 38–44.

4. Jardim-BotelhoA, RaffS, Rodrigues RdeA, HoffmanHJ, DiemertDJ, et al. (2008) Hookworm, Ascaris lumbricoides infection and polyparasitism associated with poor cognitive performance in Brazilian schoolchildren. Trop Med Int Health 13: 994–1004.

5. MarslandBJ, KurrerM, ReissmannR, HarrisNL, KopfM (2008) Nippostrongylus brasiliensis infection leads to the development of emphysema associated with the induction of alternatively activated macrophages. Eur J Immunol 38: 479–488.

6. MuroA, Perez-ArellanoJL (2010) Nitric oxide and respiratory helminthic diseases. J Biomed Biotechnol 2010: 958108.

7. HarvieM, CamberisM, TangSC, DelahuntB, PaulW, et al. (2010) The lung is an important site for priming CD4 T cell mediated protective immunity against gastrointestinal helminth parasites. Infect Immun 78 (9) 3753–62.

8. WrightV, BickleQ (2005) Immune responses following experimental human hookworm infection. Clin Exp Immunol 142: 398–403.

9. TurnerJD, FaulknerH, KamgnoJ, CormontF, Van SnickJ, et al. (2003) Th2 cytokines are associated with reduced worm burdens in a human intestinal helminth infection. J Infect Dis 188: 1768–1775.

10. FinkelmanFD, UrbanJFJr (2001) The other side of the coin: the protective role of the TH2 cytokines. J Allergy Clin Immunol 107: 772–780.

11. UrbanJFJr, Noben-TrauthN, SchopfL, MaddenKB, FinkelmanFD (2001) Cutting edge: IL-4 receptor expression by non-bone marrow-derived cells is required to expel gastrointestinal nematode parasites. J Immunol 167: 6078–6081.

12. HorsnellWG, CutlerAJ, HovingJC, MearnsH, MyburghE, et al. (2007) Delayed goblet cell hyperplasia, acetylcholine receptor expression, and worm expulsion in SMC-specific IL-4Ralpha-deficient mice. PLoS Pathog 3: e1.

13. HerbertDR, YangJQ, HoganSP, GroschwitzK, KhodounM, et al. (2009) Intestinal epithelial cell secretion of RELM-beta protects against gastrointestinal worm infection. J Exp Med 206: 2947–2957.

14. NieuwenhuizenN, HerbertDR, BrombacherF, LopataAL (2009) Differential requirements for interleukin (IL)-4 and IL-13 in protein contact dermatitis induced by Anisakis. Allergy 64: 1309–1318.

15. MearnsH, HorsnellWG, HovingJC, DewalsB, CutlerAJ, et al. (2008) Interleukin-4-promoted T helper 2 responses enhance Nippostrongylus brasiliensis-induced pulmonary pathology. Infect Immun 76: 5535–5542.

16. ThawerSG, HorsnellWG, DarbyM, HovingJC, DewalsB, et al. (2013) Lung-resident CD4 T cells are sufficient for IL-4Ralpha-dependent recall immunity to Nippostrongylus brasiliensis infection. Mucosal Immunol [epub ahead of print] doi:10.1038/mi.2013.40

17. AnthonyRM, UrbanJFJr, AlemF, HamedHA, RozoCT, et al. (2006) Memory T(H)2 cells induce alternatively activated macrophages to mediate protection against nematode parasites. Nat Med 12: 955–960.

18. MorimotoM, WhitmireJ, XiaoS, AnthonyRM, MirakamiH, et al. (2004) Peripheral CD4 T cells rapidly accumulate at the host: parasite interface during an inflammatory Th2 memory response. J Immunol 172: 2424–2430.

19. McCoyKD, StoelM, StettlerR, MerkyP, FinkK, et al. (2008) Polyclonal and specific antibodies mediate protective immunity against enteric helminth infection. Cell Host Microbe 4: 362–373.

20. LiuQ, KreiderT, BowdridgeS, LiuZ, SongY, et al. (2010) B cells have distinct roles in host protection against different nematode parasites. J Immunol 184: 5213–5223.

21. WojciechowskiW, HarrisDP, SpragueF, MousseauB, MakrisM, et al. (2009) Cytokine-producing effector B cells regulate type 2 immunity to H. polygyrus. Immunity 30: 421–433.

22. KnottML, MatthaeiKI, GiacominPR, WangH, FosterPS, et al. (2007) Impaired resistance in early secondary Nippostrongylus brasiliensis infections in mice with defective eosinophilopoeisis. Int J Parasitol 37: 1367–1378.

23. GiacominPR, GordonDL, BottoM, DahaMR, SandersonSD, et al. (2008) The role of complement in innate, adaptive and eosinophil-dependent immunity to the nematode Nippostrongylus brasiliensis. Mol Immunol 45: 446–455.

24. OhnmachtC, VoehringerD (2009) Basophil effector function and homeostasis during helminth infection. Blood 113: 2816–2825.

25. VoehringerD, ShinkaiK, LocksleyRM (2004) Type 2 immunity reflects orchestrated recruitment of cells committed to IL-4 production. Immunity 20: 267–277.

26. HovingJC, KirsteinF, NieuwenhuizenNE, FickLC, HobeikaE, et al. (2011) B Cells That Produce Immunoglobulin E Mediate Colitis in BALB/c Mice. Gastroenterology 142 (1) 96–108.

27. ChappellCP, DravesKE, GiltiayNV, ClarkEA (2012) Extrafollicular B cell activation by marginal zone dendritic cells drives T cell-dependent antibody responses. J Exp Med 209: 1825–1840.

28. Flores-LangaricaA, MarshallJL, BobatS, MohrE, HitchcockJ, et al. (2011) T-zone localized monocyte-derived dendritic cells promote Th1 priming to Salmonella. Eur J Immunol 41: 2654–2665.

29. BernasconiNL, TraggiaiE, LanzavecchiaA (2002) Maintenance of serological memory by polyclonal activation of human memory B cells. Science 298: 2199–2202.

30. JellisonER, GuayHM, Szomolanyi-TsudaE, WelshRM (2007) Dynamics and magnitude of virus-induced polyclonal B cell activation mediated by BCR-independent presentation of viral antigen. Eur J Immunol 37: 119–128.

31. PasareC, MedzhitovR (2005) Control of B-cell responses by Toll-like receptors. Nature 438: 364–368.

32. RuprechtCR, LanzavecchiaA (2006) Toll-like receptor stimulation as a third signal required for activation of human naive B cells. Eur J Immunol 36: 810–816.

33. SayiA, KohlerE, TollerIM, FlavellRA, MullerW, et al. (2011) TLR-2-activated B cells suppress Helicobacter-induced preneoplastic gastric immunopathology by inducing T regulatory-1 cells. J Immunol 186: 878–890.

34. LundFE (2008) Cytokine-producing B lymphocytes-key regulators of immunity. Curr Opin Immunol 20: 332–338.

35. HarrisDP, HaynesL, SaylesPC, DusoDK, EatonSM, et al. (2000) Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat Immunol 1: 475–482.

36. HarrisDP, GoodrichS, MohrsK, MohrsM, LundFE (2005) Cutting edge: the development of IL-4-producing B cells (B effector 2 cells) is controlled by IL-4, IL-4 receptor alpha, and Th2 cells. J Immunol 175: 7103–7107.

37. BouazizJD, YanabaK, TedderTF (2008) Regulatory B cells as inhibitors of immune responses and inflammation. Immunol Rev 224: 201–214.

38. AmuS, SaundersSP, KronenbergM, ManganNE, AtzbergerA, et al. (2010) Regulatory B cells prevent and reverse allergic airway inflammation via FoxP3-positive T regulatory cells in a murine model. J Allergy Clin Immunol 125: 1114–e1118, 1114-1124, e1118.

39. BarrTA, BrownS, MastroeniP, GrayD (2009) B cell intrinsic MyD88 signals drive IFN-gamma production from T cells and control switching to IgG2c. J Immunol 183: 1005–1012.

40. BarrTA, BrownS, MastroeniP, GrayD (2010) TLR and B cell receptor signals to B cells differentially program primary and memory Th1 responses to Salmonella enterica. J Immunol 185: 2783–2789.

41. MorrisonVL, BarrTA, BrownS, GrayD (2010) TLR-mediated loss of CD62L focuses B cell traffic to the spleen during Salmonella typhimurium infection. J Immunol 185: 2737–2746.

42. WilsonMS, TaylorMD, O'GormanMT, BalicA, BarrTA, et al. (2010) Helminth-induced CD19+CD23hi B cells modulate experimental allergic and autoimmune inflammation. Eur J Immunol 40: 1682–1696.

43. CliffeLJ, HumphreysNE, LaneTE, PottenCS, BoothC, et al. (2005) Accelerated intestinal epithelial cell turnover: a new mechanism of parasite expulsion. Science 308: 1463–1465.

44. HorsnellWG, ViraA, KirsteinF, MearnsH, HovingJC, et al. (2010) IL-4Ralpha-responsive smooth muscle cells contribute to initiation of T(H)2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections. Mucosal Immunol 4 (1) 83–92.

45. VoehringerD, ReeseTA, HuangX, ShinkaiK, LocksleyRM (2006) Type 2 immunity is controlled by IL-4/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system. J Exp Med 203: 1435–1446.

46. ZhaoA, UrbanJFJr, AnthonyRM, SunR, StiltzJ, et al. (2008) Th2 cytokine-induced alterations in intestinal smooth muscle function depend on alternatively activated macrophages. Gastroenterology 135: 217–e211, 217-225, e211.

47. MohrE, CunninghamAF, ToellnerKM, BobatS, CoughlanRE, et al. (2010) IFN-{gamma} produced by CD8 T cells induces T-bet-dependent and -independent class switching in B cells in responses to alum-precipitated protein vaccine. Proc Natl Acad Sci U S A 107: 17292–17297.

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


2013 Číslo 10
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