Interleukin-33 Increases Antibacterial Defense by Activation of Inducible Nitric Oxide Synthase in Skin

English version České info

Interleukin-33 (IL-33) is associated with multiple diseases, including asthma, rheumatoid arthritis, tissue injuries and infections. Although IL-33 has been indicated to be involved in Staphylococcus aureus (S. aureus) wound infection, little is known about how IL-33 is regulated as a mechanism to increase host defense against skin bacterial infections. To explore the underlying intricate mechanism we first evaluated the expression of IL-33 in skin from S. aureus-infected human patients. Compared to normal controls, IL-33 was abundantly increased in skin of S. aureus-infected patients. We next developed a S. aureus cutaneous infection mouse model and found that IL-33 was significantly increased in dermal macrophages of infected mouse skin. The expression of IL-33 by macrophages was induced by staphylococcal peptidoglycan (PGN) and lipoteichoic acid (LTA) via activation of toll-like receptor 2(TLR2) –mitogen-activated protein kinase (MAPK)-AKT-signal transducer and activator of transcription 3(STAT3) signaling pathway as PGN and LTA failed to induce IL-33 in Tlr2-deficient peritoneal macrophages, and MAPK,AKT, STAT3 inhibitors significantly decreased PGN- or LTA-induced IL-33. IL-33, in turn, acted on macrophages to induce microbicidal nitric oxygen (NO) release. This induction was dependent on inducible nitric oxide synthase (iNOS) activation, as treatment of macrophages with an inhibitor of iNOS, aminoguanidine, significantly decreased IL-33-induced NO release. Moreover, aminoguanidine significantly blocked the capacity of IL-33 to inhibit the growth of S. aureus, and IL-33 silencing in macrophages significantly increased the survival of S. aureus in macrophages. Furthermore, the administration of IL-33-neutralizing antibody into mouse skin decreased iNOS production but increased the survival of S. aureus in skin. These findings reveal that IL-33 can promote antimicrobial capacity of dermal macrophages, thus enhancing antimicrobial defense against skin bacterial infections.

Vyšlo v časopise: Interleukin-33 Increases Antibacterial Defense by Activation of Inducible Nitric Oxide Synthase in Skin. PLoS Pathog 10(2): e32767. doi:10.1371/journal.ppat.1003918
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003918

Souhrn

Zdroje

1. SchmitzJ, OwyangA, OldhamE, SongY, MurphyE, et al. (2005) IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23: 479–490.

2. CarriereV, RousselL, OrtegaN, LacorreDA, AmerichL, et al. (2007) IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. Proc Natl Acad Sci U S A 104: 282–287.

3. RousselL, ErardM, CayrolC, GirardJP (2008) Molecular mimicry between IL-33 and KSHV for attachment to chromatin through the H2A-H2B acidic pocket. EMBO Rep 9: 1006–1012.

4. MoussionC, OrtegaN, GirardJP (2008) The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel ‘alarmin’? PLoS One 3: e3331.

5. CayrolC, GirardJP (2009) The IL-1-like cytokine IL-33 is inactivated after maturation by caspase-1. Proc Natl Acad Sci U S A 106: 9021–9026.

6. LuthiAU, CullenSP, McNeelaEA, DuriezPJ, AfoninaIS, et al. (2009) Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases. Immunity 31: 84–98.

7. AliS, HuberM, KolleweC, BischoffSC, FalkW, et al. (2007) IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells. Proc Natl Acad Sci U S A 104: 18660–18665.

8. AllakhverdiZ, SmithDE, ComeauMR, DelespesseG (2007) Cutting edge: The ST2 ligand IL-33 potently activates and drives maturation of human mast cells. J Immunol 179: 2051–2054.

9. LiewFY, PitmanNI, McInnesIB (2010) Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat Rev Immunol 10: 103–110.

10. MirchandaniAS, SalmondRJ, LiewFY (2012) Interleukin-33 and the function of innate lymphoid cells. Trends Immunol 33: 389–396.

11. YasudaK, MutoT, KawagoeT, MatsumotoM, SasakiY, et al. (2012) Contribution of IL-33-activated type II innate lymphoid cells to pulmonary eosinophilia in intestinal nematode-infected mice. Proc Natl Acad Sci U S A 109: 3451–3456.

12. YinH, LiX, HuS, LiuT, YuanB, et al. (2013) IL-33 promotes Staphylococcus aureus-infected wound healing in mice. Int Immunopharmacol 17: 432–438.

13. KlevensRM, MorrisonMA, NadleJ, PetitS, GershmanK, et al. (2007) Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 298: 1763–1771.

14. MillerLS, ChoJS (2011) Immunity against Staphylococcus aureus cutaneous infections. Nat Rev Immunol 11: 505–518.

15. ChoJS, PietrasEM, GarciaNC, RamosRI, FarzamDM, et al. (2010) IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice. J Clin Invest 120: 1762–1773.

16. OlaruF, JensenLE (2010) Staphylococcus aureus stimulates neutrophil targeting chemokine expression in keratinocytes through an autocrine IL-1alpha signaling loop. J Invest Dermatol 130: 1866–1876.

17. KinoshitaM, MiyazakiH, OnoS, InatsuA, NakashimaH, et al. (2011) Enhancement of neutrophil function by interleukin-18 therapy protects burn-injured mice from methicillin-resistant Staphylococcus aureus. Infect Immun 79: 2670–2680.

18. HumphreysNE, XuD, HepworthMR, LiewFY, GrencisRK (2008) IL-33, a potent inducer of adaptive immunity to intestinal nematodes. J Immunol 180: 2443–2449.

19. CorbettJA, McDanielML (1995) Intraislet release of interleukin 1 inhibits beta cell function by inducing beta cell expression of inducible nitric oxide synthase. J Exp Med 181: 559–568.

20. KannoK, HirataY, ImaiT, IwashinaM, MarumoF (1994) Regulation of inducible nitric oxide synthase gene by interleukin-1 beta in rat vascular endothelial cells. Am J Physiol 267: H2318–2324.

21. ChoiYS, ChoiHJ, MinJK, PyunBJ, MaengYS, et al. (2009) Interleukin-33 induces angiogenesis and vascular permeability through ST2/TRAF6-mediated endothelial nitric oxide production. Blood 114: 3117–3126.

22. BeckermanKP, RogersHW, CorbettJA, SchreiberRD, McDanielML, et al. (1993) Release of nitric oxide during the T cell-independent pathway of macrophage activation. Its role in resistance to Listeria monocytogenes. J Immunol 150: 888–895.

23. GreenSJ, MeltzerMS, HibbsJBJr, NacyCA (1990) Activated macrophages destroy intracellular Leishmania major amastigotes by an L-arginine-dependent killing mechanism. J Immunol 144: 278–283.

24. OrmerodAD, ShahAA, LiH, BenjaminNB, FergusonGP, et al. (2011) An observational prospective study of topical acidified nitrite for killing methicillin-resistant Staphylococcus aureus (MRSA) in contaminated wounds. BMC Res Notes 4: 458.

25. FosterTJ (2005) Immune evasion by staphylococci. Nat Rev Microbiol 3: 948–958.

26. SilvaMT (2010) When two is better than one: macrophages and neutrophils work in concert in innate immunity as complementary and cooperative partners of a myeloid phagocyte system. J Leukoc Biol 87: 93–106.

27. BorregaardN, CowlandJB (1997) Granules of the human neutrophilic polymorphonuclear leukocyte. Blood 89: 3503–3521.

28. SegalAW (2005) How neutrophils kill microbes. Annu Rev Immunol 23: 197–223.

29. SilvaMT, Correia-NevesM (2012) Neutrophils and macrophages: the main partners of phagocyte cell systems. Front Immunol 3: 174.

30. CartaS, LavieriR, RubartelliA (2013) Different Members of the IL-1 Family Come Out in Different Ways: DAMPs vs. Cytokines? Front Immunol 4: 123.

31. KouzakiH, IijimaK, KobayashiT, O'GradySM, KitaH (2011) The danger signal, extracellular ATP, is a sensor for an airborne allergen and triggers IL-33 release and innate Th2-type responses. J Immunol 186: 4375–4387.

32. LefrancaisE, RogaS, GautierV, Gonzalez-de-PeredoA, MonsarratB, et al. (2012) IL-33 is processed into mature bioactive forms by neutrophil elastase and cathepsin G. Proc Natl Acad Sci U S A 109: 1673–1678.

33. Kurowska-StolarskaM, KewinP, MurphyG, RussoRC, StolarskiB, et al. (2008) IL-33 induces antigen-specific IL-5+ T cells and promotes allergic-induced airway inflammation independent of IL-4. J Immunol 181: 4780–4790.

34. Alves-FilhoJC, SonegoF, SoutoFO, FreitasA, VerriWAJr, et al. (2010) Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection. Nat Med 16: 708–712.

35. PushparajPN, TayHK, H'NgSC, PitmanN, XuD, et al. (2009) The cytokine interleukin-33 mediates anaphylactic shock. Proc Natl Acad Sci U S A 106: 9773–9778.

36. GhaffariA, JaliliR, GhaffariM, MillerC, GhaharyA (2007) Efficacy of gaseous nitric oxide in the treatment of skin and soft tissue infections. Wound Repair Regen 15: 368–377.

37. GhaffariA, MillerCC, McMullinB, GhaharyA (2006) Potential application of gaseous nitric oxide as a topical antimicrobial agent. Nitric Oxide 14: 21–29.

38. WangR, GhaharyA, ShenYJ, ScottPG, TredgetEE (1996) Human dermal fibroblasts produce nitric oxide and express both constitutive and inducible nitric oxide synthase isoforms. J Invest Dermatol 106: 419–427.

39. MannickJB, AsanoK, IzumiK, KieffE, StamlerJS (1994) Nitric oxide produced by human B lymphocytes inhibits apoptosis and Epstein-Barr virus reactivation. Cell 79: 1137–1146.

40. XieQW, ChoHJ, CalaycayJ, MumfordRA, SwiderekKM, et al. (1992) Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science 256: 225–228.

41. VouldoukisI, Riveros-MorenoV, DugasB, OuaazF, BecherelP, et al. (1995) The killing of Leishmania major by human macrophages is mediated by nitric oxide induced after ligation of the Fc epsilon RII/CD23 surface antigen. Proc Natl Acad Sci U S A 92: 7804–7808.

42. MacMickingJ, XieQW, NathanC (1997) Nitric oxide and macrophage function. Annu Rev Immunol 15: 323–350.

43. GongK, ZhouF, HuangH, GongY, ZhangL (2012) Suppression of GSK3beta by ERK mediates lipopolysaccharide induced cell migration in macrophage through beta-catenin signaling. Protein Cell 3: 762–768.

44. LaiY, Di NardoA, NakatsujiT, LeichtleA, YangY, et al. (2009) Commensal bacteria regulate Toll-like receptor 3-dependent inflammation after skin injury. Nat Med 15: 1377–1382.

45. LaiY, LiD, LiC, MuehleisenB, RadekKA, et al. (2012) The antimicrobial protein REG3A regulates keratinocyte proliferation and differentiation after skin injury. Immunity 37: 74–84.

46. WeischenfeldtJ, PorseB (2008) Bone Marrow-Derived Macrophages (BMM): Isolation and Applications. CSH Protoc 2008 pdb prot5080.

47. DykhuizenRS, FrazerR, DuncanC, SmithCC, GoldenM, et al. (1996) Antimicrobial effect of acidified nitrite on gut pathogens: importance of dietary nitrate in host defense. Antimicrob Agents Chemother 40: 1422–1425.

48. HuckerGJ (1921) A New Modification and Application of the Gram Stain. J Bacteriol 6: 395–397.