#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Hypercytotoxicity and Rapid Loss of NKp44 Innate Lymphoid Cells during Acute SIV Infection


HIV-1 has long been shown to deplete CD4+ T cells and disrupt barrier integrity in the gastrointestinal tract, but effects on other subpopulations of lymphocytes are less well described. A recently identified subpopulation of mucosa-restricted cells, termed innate lymphoid cells (ILCs) is thought to play critical roles in maintaining homeostasis in the gastrointestinal tract and mucosal pathogen defense. Although previous work from our laboratory and others have shown SIV infection of rhesus macaques can deplete ILCs in some parts of the gastrointestinal tract, systemic as well as kinetic effects were unclear. In this report we show that ILCs, but not classical NK cells are systemically depleted during infection and also acquire cytotoxic capabilities. Furthermore, our data is the first to indicate that this important subset of innate cells is depleted acutely, permanently, and systemically during SIV infection of rhesus macaques as a model for HIV-1 infection. Given the important role of ILCs in maintaining gut homeostasis these findings could have significant implications for the understanding and treatment of HIV-induced disease.


Vyšlo v časopise: Hypercytotoxicity and Rapid Loss of NKp44 Innate Lymphoid Cells during Acute SIV Infection. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004551
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004551

Souhrn

HIV-1 has long been shown to deplete CD4+ T cells and disrupt barrier integrity in the gastrointestinal tract, but effects on other subpopulations of lymphocytes are less well described. A recently identified subpopulation of mucosa-restricted cells, termed innate lymphoid cells (ILCs) is thought to play critical roles in maintaining homeostasis in the gastrointestinal tract and mucosal pathogen defense. Although previous work from our laboratory and others have shown SIV infection of rhesus macaques can deplete ILCs in some parts of the gastrointestinal tract, systemic as well as kinetic effects were unclear. In this report we show that ILCs, but not classical NK cells are systemically depleted during infection and also acquire cytotoxic capabilities. Furthermore, our data is the first to indicate that this important subset of innate cells is depleted acutely, permanently, and systemically during SIV infection of rhesus macaques as a model for HIV-1 infection. Given the important role of ILCs in maintaining gut homeostasis these findings could have significant implications for the understanding and treatment of HIV-induced disease.


Zdroje

1. BrenchleyJM, SchackerTW, RuffLE, PriceDA, TaylorJH, et al. (2004) CD4+T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 200: 749–759.

2. SankaranS, GuadalupeM, ReayE, GeorgeMD, FlammJ, et al. (2005) Gut mucosal T cell responses and gene expression correlate with protection against disease in long-term HIV-1-infected nonprogressors. Proc Natl Acad Sci U S A 102: 9860–9865.

3. LiQ, DuanL, EstesJD, MaZM, RourkeT, et al. (2005) Peak SIV replication in resting memory CD4+T cells depletes gut lamina propria CD4+T cells. Nature 434: 1148–1152.

4. VeazeyRS, DeMariaM, ChalifouxLV, ShvetzD, PauleyD, et al. (1998) The gastrointestinal tract as a major site of CD4 T lymphocyte depletion and viral replication in SIV infection. Science 280: 427–431.

5. HaaseAT (2010) Targeting early infection to prevent HIV-1 mucosal transmission. Nature 464: 217–223.

6. MattapallilJJ, DouekDC, HillBJ, NishimuraY, MartinM, et al. (2005) Massive infection and loss of memory CD4+T cells in multiple tissues during acute SIV infection. Nature 434: 1093–1097.

7. VeazeyRS, ThamIC, MansfieldKG, DeMariaM, ForandAE, et al. (2000) Indentifying the target cell in primary simian immunodeficiency virus (SIV) infection: highly activated memory CD4+T cells are rapidly eliminated in early SIV infection in vivo. J Virol 74: 57–64.

8. SpitsH, CupedoT (2012) Innate lymphoid cells: emerging insights in development, lineage relationships, and function. Annu Rev Immunol 30: 647–675.

9. SpitsH, Di SantoJP (2011) The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling. Nat Immunol 12: 21–27.

10. Satoh-TakayamaN, VosshenrichCA, Lesjean-PottierS, SawaS, LochnerM, et al. (2008) Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 29: 958–970.

11. SonnenbergGF, MonticelliLA, EllosoMM, FouserLA, ArtisD (2011) CD4(+) lymphoid tissue-inducer cells promote innate immunity in the gut. Immunity 34: 122–134.

12. ZhengY, ValdezPA, DanilenkoDM, HuY, SaSM, et al. (2008) Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 14: 282–289.

13. MoroK, YamadaT, TanabeM, TakeuchiT, IkawaT, et al. (2010) Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature 463: 540–544.

14. BoosMD, YokotaY, EberlG, KeeBL (2007) Mature natural killer cell and lymphoid tissue-inducing cell development requires Id2-mediated suppression of E protein activity. J Exp Med 204: 1119–1130.

15. SchmutzS, BoscoN, ChappazS, BoymanO, Acha-OrbeaH, et al. (2009) Cutting edge: IL-7 regulates the peripheral pool of adult ROR gamma+ lymphoid tissue inducer cells. J Immunol 183: 2217–2221.

16. Satoh-TakayamaN, Lesjean-PottierS, VieiraP, SawaS, EberlG, et al. (2010) IL-7 and IL-15 independently program the differentiation of intestinal CD3-NKp46+ cell subsets from Id2-dependent precursors. J Exp Med 207: 273–280.

17. GordonSM, ChaixJ, RuppLJ, WuJ, MaderaS, et al. (2012) The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation. Immunity 36: 55–67.

18. CellaM, FuchsA, VermiW, FacchettiF, OteroK, et al. (2009) A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 457: 722–725.

19. TakatoriH, KannoY, WatfordWT, TatoCM, WeissG, et al. (2009) Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J Exp Med 206: 35–41.

20. SpitsH, ArtisD, ColonnaM, DiefenbachA, Di SantoJP, et al. (2013) Innate lymphoid cells—a proposal for uniform nomenclature. Nat Rev Immunol 13: 145–149.

21. HoylerT, KloseCS, SouabniA, Turqueti-NevesA, PfeiferD, et al. (2012) The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells. Immunity 37: 634–648.

22. MjosbergJ, BerninkJ, GolebskiK, KarrichJJ, PetersCP, et al. (2012) The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells. Immunity 37: 649–659.

23. ReevesRK, RajakumarPA, EvansTI, ConnoleM, GillisJ, et al. (2011) Gut inflammation and indoleamine deoxygenase inhibit IL-17 production and promote cytotoxic potential in NKp44+ mucosal NK cells during SIV infection. Blood 118: 3321–3330.

24. XuH, WangX, LiuDX, Moroney-RasmussenT, LacknerAA, et al. (2012) IL-17-producing innate lymphoid cells are restricted to mucosal tissues and are depleted in SIV-infected macaques. Mucosal Immunol 5: 658–669.

25. KlattNR, EstesJD, SunX, OrtizAM, BarberJS, et al. (2012) Loss of mucosal CD103+ DCs and IL-17+ and IL-22+ lymphocytes is associated with mucosal damage in SIV infection. Mucosal Immunol 5: 646–657.

26. KhowawisetsutL, PattanapanyasatK, OnlamoonN, MayneAE, LittleDM, et al. (2013) Relationships between IL-17(+) subsets, Tregs and pDCs that distinguish among SIV infected elite controllers, low, medium and high viral load rhesus macaques. PLoS One 8: e61264.

27. LiyanageNP, GordonSN, DosterMN, PeguP, VaccariM, et al. (2014) Antiretroviral therapy partly reverses the systemic and mucosal distribution of NK cell subsets that is altered by SIVmac(2)(5)(1) infection of macaques. Virology 450–451: 359–368.

28. Scott-AlgaraD, TruongLX, VersmisseP, DavidA, LuongTT, et al. (2003) Cutting edge: increased NK cell activity in HIV-1-exposed but uninfected Vietnamese intravascular drug users. J Immunol 171: 5663–5667.

29. TomescuC, DuhFM, HohR, VivianiA, HarvillK, et al. (2012) Impact of protective killer inhibitory receptor/human leukocyte antigen genotypes on natural killer cell and T-cell function in HIV-1-infected controllers. AIDS 26: 1869–1878.

30. PancinoG, Saez-CirionA, Scott-AlgaraD, PaulP (2010) Natural resistance to HIV infection: lessons learned from HIV-exposed uninfected individuals. J Infect Dis 202 Suppl 3S345–350.

31. TomescuC, DuhFM, LanierMA, KapalkoA, MounzerKC, et al. (2010) Increased plasmacytoid dendritic cell maturation and natural killer cell activation in HIV-1 exposed, uninfected intravenous drug users. AIDS 24: 2151–2160.

32. RavetS, Scott-AlgaraD, BonnetE, TranHK, TranT, et al. (2007) Distinctive NK-cell receptor repertoires sustain high-level constitutive NK-cell activation in HIV-exposed uninfected individuals. Blood 109: 4296–4305.

33. Flores-VillanuevaPO, YunisEJ, DelgadoJC, VittinghoffE, BuchbinderS, et al. (2001) Control of HIV-1 viremia and protection from AIDS are associated with HLA-Bw4 homozygosity. Proc Natl Acad Sci U S A 98: 5140–5145.

34. AlterG, MartinMP, TeigenN, CarrWH, SuscovichTJ, et al. (2007) Differential natural killer cell-mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes. J Exp Med 204: 3027–3036.

35. O'ConnellKA, HanY, WilliamsTM, SilicianoRF, BlanksonJN (2009) Role of natural killer cells in a cohort of elite suppressors: low frequency of the protective KIR3DS1 allele and limited inhibition of human immunodeficiency virus type 1 replication in vitro. J Virol 83: 5028–5034.

36. ElemansM, ThiebautR, KaurA, AsquithB (2011) Quantification of the relative importance of CTL, B cell, NK cell, and target cell limitation in the control of primary SIV-infection. PLoS Comput Biol 7: e1001103.

37. ReevesRK, GillisJ, WongFE, YuY, ConnoleM, et al. (2010) CD16- natural killer cells: enrichment in mucosal and secondary lymphoid tissues and altered function during chronic SIV infection. Blood 115: 4439–4446.

38. Abdel-MotalUM, GillisJ, MansonK, WyandM, MontefioriD, et al. (2005) Kinetics of expansion of SIV Gag-specific CD8+T lymphocytes following challenge of vaccinated macaques. Virology 333: 226–238.

39. ReevesRK, GillisJ, WongFE, JohnsonRP (2009) Vaccination with SIVmac239Deltanef activates CD4+T cells in the absence of CD4 T-cell loss. J Med Primatol 38 Suppl 18–16.

40. GiavedoniLD (2005) Simultaneous detection of multiple cytokines and chemokines from nonhuman primates using luminex technology. Journal of Immunological Methods 301: 89–101.

41. ClineAN, BessJW, PiatakMJr, LifsonJD (2005) Highly sensitive SIV plasma viral load assay: practical considerations, realistic performance expectations, and application to reverse engineering of vaccines for AIDS. J Med Primatol 34: 303–312.

42. HansenSG, PiatakMJr, VenturaAB, HughesCM, GilbrideRM, et al. (2013) Immune clearance of highly pathogenic SIV infection. Nature 502: 100–104.

43. ReevesRK, EvansTI, GillisJ, JohnsonRP (2010) Simian immunodeficiency virus infection induces expansion of alpha4beta7+ and cytotoxic CD56+ NK cells. J Virol 84: 8959–8963.

44. ReevesRK, EvansTI, GillisJ, WongFE, KangG, et al. (2012) SIV infection induces accumulation of plasmacytoid dendritic cells in the gut mucosa. J Infect Dis 206: 1462–1468.

45. EstesJD, HarrisLD, KlattNR, TabbB, PittalugaS, et al. (2010) Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. PLoS Pathog 6. DOI:10.1371/journal.ppat.1001052

46. KlattNR, FunderburgNT, BrenchleyJM (2013) Microbial translocation, immune activation, and HIV disease. Trends Microbiol 21: 6–13.

47. MorthaA, ChudnovskiyA, HashimotoD, BogunovicM, SpencerSP, et al. (2014) Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science 343: 1249288.

48. KloseCS, KissEA, SchwierzeckV, EbertK, HoylerT, et al. (2013) A T-bet gradient controls the fate and function of CCR6-RORgammat+ innate lymphoid cells. Nature 494: 261–265.

49. BuonocoreS, AhernPP, UhligHH, Ivanov, II, LittmanDR, et al. (2010) Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature 464: 1371–1375.

50. FuchsA, ColonnaM (2013) Innate lymphoid cells in homeostasis, infection, chronic inflammation and tumors of the gastrointestinal tract. Curr Opin Gastroenterol 29: 581–587.

51. AlterG, TeigenN, DavisBT, AddoMM, SuscovichTJ, et al. (2005) Sequential deregulation of NK cell subset distribution and function starting in acute HIV-1 infection. Blood 106: 3366–3369.

52. AlterG, TeigenN, AhernR, StreeckH, MeierA, et al. (2007) Evolution of innate and adaptive effector cell functions during acute HIV-1 infection. J Infect Dis 195: 1452–1460.

53. ChoiEI, ReimannKA, LetvinNL (2008) In vivo natural killer cell depletion during primary simian immunodeficiency virus infection in rhesus monkeys. Journal of Virology 82: 6758–6761.

54. ChoiEI, WangR, PetersonL, LetvinNL, ReimannKA (2008) Use of an anti-CD16 antibody for in vivo depletion of natural killer cells in rhesus macaques. Immunology 124: 215–222.

55. FehnigerTA, HerbeinG, YuH, ParaMI, BernsteinZP, et al. (1998) Natural killer cells from HIV-1+ patients produce C-C chemokines and inhibit HIV-1 infection. J Immunol 161: 6433–6438.

56. O'ConnorGM, HolmesA, MulcahyF, GardinerCM (2007) Natural killer cells from long-term non-progressor HIV patients are characterized by altered phenotype and function. Clin Immunol 124: 277–283.

57. GiavedoniLD, VelasquilloMC, ParodiLM, HubbardGB, HodaraVL (2000) Cytokine expression, natural killer cell activation, and phenotypic changes in lymphoid cells from rhesus macaques during acute infection with pathogenic simian immunodeficiency virus. J Virol 74: 1648–1657.

58. ShiehTM, CarterDL, BlosserRL, MankowskiJL, ZinkMC, et al. (2001) Functional analyses of natural killer cells in macaques infected with neurovirulent simian immunodeficiency virus. J Neurovirol 7: 11–24.

59. BostikP, KobkitjaroenJ, TangW, VillingerF, PereiraLE, et al. (2009) Decreased NK cell frequency and function is associated with increased risk of KIR3DL allele polymorphism in simian immunodeficiency virus-infected rhesus macaques with high viral loads. J Immunol 182: 3638–3649.

60. GonzalezVD, FalconerK, MichaelssonJ, MollM, ReichardO, et al. (2008) Expansion of CD56- NK cells in chronic HCV/HIV-1 co-infection: reversion by antiviral treatment with pegylated IFNalpha and ribavirin. Clin Immunol 128: 46–56.

61. MarrasF, NiccoE, BozzanoF, Di BiagioA, DentoneC, et al. (2013) Natural killer cells in HIV controller patients express an activated effector phenotype and do not up-regulate NKp44 on IL-2 stimulation. Proc Natl Acad Sci U S A 110: 11970–11975.

62. MichaelssonJ, LongBR, LooCP, LanierLL, SpottsG, et al. (2008) Immune reconstitution of CD56(dim) NK cells in individuals with primary HIV-1 infection treated with interleukin-2. J Infect Dis 197: 117–125.

63. KamyaP, BouletS, TsoukasCM, RoutyJP, ThomasR, et al. (2011) Receptor-ligand requirements for increased NK cell polyfunctional potential in slow progressors infected with HIV-1 coexpressing KIR3DL1*h/*y and HLA-B*57. J Virol 85: 5949–5960.

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2014 Číslo 12
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#