The Triggering Receptor Expressed on Myeloid Cells 2 Inhibits Complement Component 1q Effector Mechanisms and Exerts Detrimental Effects during Pneumococcal Pneumonia

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Bacterial respiratory tract infections are a major cause of morbidity and mortality, and Streptococcus pneumoniae (S. pneumoniae) remains the main cause of community acquired pneumonia worldwide. The continued rise in antibiotic resistance stresses the need for better insights into the host defense mechanisms associated with pneumococcal pneumonia. The early innate immune response that constitutes bacterial phagocytosis, complement activation and inflammation is critical for the outcome during pneumonia. The triggering receptor expressed on myeloid cells 2 (TREM-2) has recently been shown to be both a negative regulator of the inflammatory response and a promoter of phagocytosis, but its contribution to pneumonia remains unknown. In our study, we unexpectedly found that alveolar macrophage expressed TREM-2 is detrimental in bacterial phagocytosis and clearance during pneumococcal pneumonia. This occurred via the suppressive effects of TREM-2 on complement component 1q (C1q), an important regulator of bacterial phagocytosis that is crucial for the host response during pneumonia. Thus, targeting the TREM-2 pathway could be used as a novel strategy for modulating C1q production and pulmonary innate immune responses, which could be of clinical relevance during pneumonia and other respiratory tract infections.

Vyšlo v časopise: The Triggering Receptor Expressed on Myeloid Cells 2 Inhibits Complement Component 1q Effector Mechanisms and Exerts Detrimental Effects during Pneumococcal Pneumonia. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004167
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004167

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1. UnderhillDM, OzinskyA, HajjarAM, StevensA, WilsonCB, et al. (1999) The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 401 : 811–815.

2. IpWK, SokolovskaA, CharriereGM, BoyerL, DejardinS, et al. (2010) Phagocytosis and phagosome acidification are required for pathogen processing and MyD88-dependent responses to Staphylococcus aureus. J Immunol 184 : 7071–7081.

3. WolfAJ, ArrudaA, ReyesCN, KaplanAT, ShimadaT, et al. (2011) Phagosomal degradation increases TLR access to bacterial ligands and enhances macrophage sensitivity to bacteria. J Immunol 187 : 6002–6010.

4. FitzgeraldML, MooreKJ, FreemanMW, ReedGL (2000) Lipopolysaccharide induces scavenger receptor A expression in mouse macrophages: a divergent response relative to human THP-1 monocyte/macrophages. J Immunol 164 : 2692–2700.

5. van der LaanLJ, KangasM, DoppEA, Broug-HolubE, ElomaaO, et al. (1997) Macrophage scavenger receptor MARCO: in vitro and in vivo regulation and involvement in the anti-bacterial host defense. Immunol Lett 57 : 203–208.

6. McIntoshJC, SwyersAH, FisherJH, WrightJR (1996) Surfactant proteins A and D increase in response to intratracheal lipopolysaccharide. Am J Respir Cell Mol Biol 15 : 509–519.

7. ZhouAQ, HerriottMJ, LeuRW (1991) Kinetics of the biosynthesis of complement subcomponent C1q by murine macrophages: LPS, immune complexes, and zymosan alone and in combination with interferon-gamma. J Leukoc Biol 50 : 453–463.

8. SharifO, KnappS (2008) From expression to signaling: roles of TREM-1 and TREM-2 in innate immunity and bacterial infection. Immunobiology 213 : 701–713.

9. FordJW, McVicarDW (2009) TREM and TREM-like receptors in inflammation and disease. Curr Opin Immunol 21 : 38–46.

10. TurnbullIR, GilfillanS, CellaM, AoshiT, MillerM, et al. (2006) Cutting edge: TREM-2 attenuates macrophage activation. J Immunol 177 : 3520–3524.

11. TakahashiK, RochfordCD, NeumannH (2005) Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. J Exp Med 201 : 647–657.

12. CellaM, BuonsantiC, StraderC, KondoT, SalmaggiA, et al. (2003) Impaired differentiation of osteoclasts in TREM-2-deficient individuals. J Exp Med 198 : 645–651.

13. KlunemannHH, RidhaBH, MagyL, WherrettJR, HemelsoetDM, et al. (2005) The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2. Neurology 64 : 1502–1507.

14. NeumannH, DalyMJ (2013) Variant TREM2 as risk factor for Alzheimer's disease. N Engl J Med 368 : 182–184.

15. GuerreiroR, WojtasA, BrasJ, CarrasquilloM, RogaevaE, et al. (2013) TREM2 variants in Alzheimer's disease. N Engl J Med 368 : 117–127.

16. TurnbullIR, ColonnaM (2007) Activating and inhibitory functions of DAP12. Nat Rev Immunol 7 : 155–161.

17. BouchonA, FacchettiF, WeigandMA, ColonnaM (2001) TREM-1 amplifies inflammation and is a crucial mediator of septic shock. Nature 410 : 1103–1107.

18. BleharskiJR, KiesslerV, BuonsantiC, SielingPA, StengerS, et al. (2003) A role for triggering receptor expressed on myeloid cells-1 in host defense during the early-induced and adaptive phases of the immune response. J Immunol 170 : 3812–3818.

19. LaglerH, SharifO, HaslingerI, MattU, StichK, et al. (2009) TREM-1 activation alters the dynamics of pulmonary IRAK-M expression in vivo and improves host defense during pneumococcal pneumonia. J Immunol 183 : 2027–2036.

20. HamermanJA, JarjouraJR, HumphreyMB, NakamuraMC, SeamanWE, et al. (2006) Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12. J Immunol 177 : 2051–2055.

21. N'DiayeEN, BrandaCS, BrandaSS, NevarezL, ColonnaM, et al. (2009) TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic receptor for bacteria. J Cell Biol 184 : 215–223.

22. ChenQ, ZhangK, JinY, ZhuT, ChengB, et al. (2013) Triggering Receptor Expressed on Myeloid Cells-2 Protects against Polymicrobial Sepsis by Enhancing Bacterial Clearance. Am J Respir Crit Care Med 188 : 201–212.

23. van der PollT, OpalSM (2009) Pathogenesis, treatment, and prevention of pneumococcal pneumonia. Lancet 374 : 1543–1556.

24. LiJ, PritchardDK, WangX, ParkDR, BumgarnerRE, et al. (2007) cDNA microarray analysis reveals fundamental differences in the expression profiles of primary human monocytes, monocyte-derived macrophages, and alveolar macrophages. J Leukoc Biol 81 : 328–335.

25. SunGY, GuanCX, ZhouY, LiuYP, LiSF, et al. (2011) Vasoactive intestinal peptide re-balances TREM-1/TREM-2 ratio in acute lung injury. Regul Pept 167 : 56–64.

26. AokiN, ZganiaczA, MargettsP, XingZ (2004) Differential regulation of DAP12 and molecules associated with DAP12 during host responses to mycobacterial infection. Infect Immun 72 : 2477–2483.

27. RijneveldAW, FlorquinS, BrangerJ, SpeelmanP, Van DeventerSJ, et al. (2001) TNF-alpha compensates for the impaired host defense of IL-1 type I receptor-deficient mice during pneumococcal pneumonia. J Immunol 167 : 5240–5246.

28. van der PollT, KeoghCV, BuurmanWA, LowrySF (1997) Passive immunization against tumor necrosis factor-alpha impairs host defense during pneumococcal pneumonia in mice. Am J Respir Crit Care Med 155 : 603–608.

29. ArredouaniM, YangZ, NingY, QinG, SoininenR, et al. (2004) The scavenger receptor MARCO is required for lung defense against pneumococcal pneumonia and inhaled particles. J Exp Med 200 : 267–272.

30. BrownJS, HussellT, GillilandSM, HoldenDW, PatonJC, et al. (2002) The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice. Proc Natl Acad Sci U S A 99 : 16969–16974.

31. WikenheiserKA, VorbrokerDK, RiceWR, ClarkJC, BachurskiCJ, et al. (1993) Production of immortalized distal respiratory epithelial cell lines from surfactant protein C/simian virus 40 large tumor antigen transgenic mice. Proc Natl Acad Sci U S A 90 : 11029–11033.

32. HumphreyMB, DawsMR, SpustaSC, NiemiEC, TorchiaJA, et al. (2006) TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function. J Bone Miner Res 21 : 237–245.

33. ZengH, OrnatowskaM, JooMS, SadikotRT (2007) TREM-1 expression in macrophages is regulated at transcriptional level by NF-kappaB and PU.1. Eur J Immunol 37 : 2300–2308.

34. WunderlichP, GlebovK, KemmerlingN, TienNT, NeumannH, et al. (2013) Sequential proteolytic processing of the triggering receptor expressed on myeloid cells-2 (TREM2) protein by ectodomain shedding and gamma-secretase-dependent intramembranous cleavage. J Biol Chem 288 : 33027–33036.

35. BalamayooranG, BatraS, FesslerMB, HappelKI, JeyaseelanS (2010) Mechanisms of neutrophil accumulation in the lungs against bacteria. Am J Respir Cell Mol Biol 43 : 5–16.

36. SchroderNW, MorathS, AlexanderC, HamannL, HartungT, et al. (2003) Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved. J Biol Chem 278 : 15587–15594.

37. IvashkivLB (2009) Cross-regulation of signaling by ITAM-associated receptors. Nat Immunol 10 : 340–347.

38. KaplanSL, BarsonWJ, LinPL, StovallSH, BradleyJS, et al. (2010) Serotype 19A Is the most common serotype causing invasive pneumococcal infections in children. Pediatrics 125 : 429–436.

39. SunK, MetzgerDW (2008) Inhibition of pulmonary antibacterial defense by interferon-gamma during recovery from influenza infection. Nat Med 14 : 558–564.

40. MukundanL, OdegaardJI, MorelCR, HerediaJE, MwangiJW, et al. (2009) PPAR-delta senses and orchestrates clearance of apoptotic cells to promote tolerance. Nat Med 15 : 1266–1272.

41. KapoorA, ShintaniY, CollinoM, OsuchowskiMF, BuschD, et al. (2010) Protective role of peroxisome proliferator-activated receptor-beta/delta in septic shock. Am J Respir Crit Care Med 182 : 1506–1515.

42. RabsU, MartinH, HitscholdT, GolanMD, HeinzHP, et al. (1986) Isolation and characterization of macrophage-derived C1q and its similarities to serum C1q. Eur J Immunol 16 : 1183–1186.

43. PetryF, ReidKB, LoosM (1989) Molecular cloning and characterization of the complementary DNA coding for the B-chain of murine Clq. FEBS Lett 258 : 89–93.

44. KaulM, LoosM (1995) Collagen-like complement component C1q is a membrane protein of human monocyte-derived macrophages that mediates endocytosis. J Immunol 155 : 5795–5802.

45. LuJH, TehBK, WangL, WangYN, TanYS, et al. (2008) The classical and regulatory functions of C1q in immunity and autoimmunity. Cell Mol Immunol 5 : 9–21.

46. PetryF, BottoM, HoltappelsR, WalportMJ, LoosM (2001) Reconstitution of the complement function in C1q-deficient (C1qa−/−) mice with wild-type bone marrow cells. J Immunol 167 : 4033–4037.

47. BottoM, Dell'AgnolaC, BygraveAE, ThompsonEM, CookHT, et al. (1998) Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet 19 : 56–59.

48. OgdenCA, deCathelineauA, HoffmannPR, BrattonD, GhebrehiwetB, et al. (2001) C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. J Exp Med 194 : 781–795.

49. VandivierRW, OgdenCA, FadokVA, HoffmannPR, BrownKK, et al. (2002) Role of surfactant proteins A, D, and C1q in the clearance of apoptotic cells in vivo and in vitro: calreticulin and CD91 as a common collectin receptor complex. J Immunol 169 : 3978–3986.

50. RupprechtTA, AngeleB, KleinM, HeesemannJ, PfisterHW, et al. (2007) Complement C1q and C3 are critical for the innate immune response to Streptococcus pneumoniae in the central nervous system. J Immunol 178 : 1861–1869.

51. ZipfelPF, SkerkaC (2009) Complement regulators and inhibitory proteins. Nat Rev Immunol 9 : 729–740.

52. AgarwalV, AhlJ, RiesbeckK, BlomAM (2013) An alternative role of C1q in bacterial infections: facilitating Streptococcus pneumoniae adherence and invasion of host cells. J Immunol 191 : 4235–4245.

53. KnappS, LeemansJC, FlorquinS, BrangerJ, MarisNA, et al. (2003) Alveolar macrophages have a protective antiinflammatory role during murine pneumococcal pneumonia. Am J Respir Crit Care Med 167 : 171–179.

54. CoxG, CrossleyJ, XingZ (1995) Macrophage engulfment of apoptotic neutrophils contributes to the resolution of acute pulmonary inflammation in vivo. Am J Respir Cell Mol Biol 12 : 232–237.

55. MarriottHM, HellewellPG, CrossSS, IncePG, WhyteMK, et al. (2006) Decreased alveolar macrophage apoptosis is associated with increased pulmonary inflammation in a murine model of pneumococcal pneumonia. J Immunol 177 : 6480–6488.

56. PoonIK, LucasCD, RossiAG, RavichandranKS (2014) Apoptotic cell clearance: basic biology and therapeutic potential. Nat Rev Immunol 14 : 166–180.

57. KangYS, DoY, LeeHK, ParkSH, CheongC, et al. (2006) A dominant complement fixation pathway for pneumococcal polysaccharides initiated by SIGN-R1 interacting with C1q. Cell 125 : 47–58.

58. KnappS, WielandCW, van't VeerC, TakeuchiO, AkiraS, et al. (2004) Toll-like receptor 2 plays a role in the early inflammatory response to murine pneumococcal pneumonia but does not contribute to antibacterial defense. J Immunol 172 : 3132–3138.

59. Bishop-BaileyD, BystromJ (2009) Emerging roles of peroxisome proliferator-activated receptor-beta/delta in inflammation. Pharmacol Ther 124 : 141–150.

60. Bishop-BaileyD, HlaT (1999) Endothelial cell apoptosis induced by the peroxisome proliferator-activated receptor (PPAR) ligand 15-deoxy-Delta12, 14-prostaglandin J2. J Biol Chem 274 : 17042–17048.

61. BouchonA, Hernandez-MunainC, CellaM, ColonnaM (2001) A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells. J Exp Med 194 : 1111–1122.

62. OteroK, ShinoharaM, ZhaoH, CellaM, GilfillanS, et al. (2012) TREM2 and beta-catenin regulate bone homeostasis by controlling the rate of osteoclastogenesis. J Immunol 188 : 2612–2621.

63. HsiehCL, KoikeM, SpustaSC, NiemiEC, YenariM, et al. (2009) A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia. J Neurochem 109 : 1144–1156.

64. CorrealeC, GenuaM, VetranoS, MazziniE, MartinoliC, et al. (2013) Bacterial sensor triggering receptor expressed on myeloid cells-2 regulates the mucosal inflammatory response. Gastroenterology 144 : 346–356 e343.

65. SieberMW, JaenischN, BrehmM, GuentherM, Linnartz-GerlachB, et al. (2013) Attenuated inflammatory response in triggering receptor expressed on myeloid cells 2 (TREM2) knock-out mice following stroke. PLoS One 8: e52982.

66. FraserDA, BohlsonSS, JasinskieneN, RawalN, PalmariniG, et al. (2006) C1q and MBL, components of the innate immune system, influence monocyte cytokine expression. J Leukoc Biol 80 : 107–116.

67. FraserDA, AroraM, BohlsonSS, LozanoE, TennerAJ (2007) Generation of inhibitory NFkappaB complexes and phosphorylated cAMP response element-binding protein correlates with the anti-inflammatory activity of complement protein C1q in human monocytes. J Biol Chem 282 : 7360–7367.

68. SchabbauerG, MattU, GunzlP, WarszawskaJ, FurtnerT, et al. (2010) Myeloid PTEN promotes inflammation but impairs bactericidal activities during murine pneumococcal pneumonia. J Immunol 185 : 468–476.

69. SharifO, MattU, SaluzzoS, LakovitsK, HaslingerI, et al. (2013) The scavenger receptor CD36 downmodulates the early inflammatory response while enhancing bacterial phagocytosis during pneumococcal pneumonia. J Immunol 190 : 5640–5648.

70. de FreitasA, BanerjeeS, XieN, CuiH, DavisKI, et al. (2012) Identification of TLT2 as an engulfment receptor for apoptotic cells. J Immunol 188 : 6381–6388.

71. IrizarryRA, BolstadBM, CollinF, CopeLM, HobbsB, et al. (2003) Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res 31: e15.

72. TusherVG, TibshiraniR, ChuG (2001) Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A 98 : 5116–5121.