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Current HIV/AIDS Reports

, Volume 15, Issue 1, pp 1–10 | Cite as

The Dual Role of Neutrophils in HIV Infection

  • Tiffany Hensley-McBain
  • Nichole R. Klatt
HIV Pathogenesis and Treatment (AL Landay and N Utay, Section Editors)
Part of the following topical collections:
  1. Topical Collection on HIV Pathogenesis and Treatment

Abstract

Purpose of Review

We summarize what is known about neutrophils in HIV infection, focusing on their potential roles in HIV protection, acquisition, and pathogenesis.

Recent Findings

Recent studies have demonstrated that neutrophil-associated proteins and cytokines in genital tissue pre-infection associate with HIV acquisition. However, recent in vivo assessment of highly exposed seronegative individuals and in vitro studies of anti-HIV functions of neutrophils add to older literature evidence that neutrophils may be important in a protective response to HIV infection.

Summary

Neutrophils are important for containment of pathogens but can also contribute to tissue damage due to their release of reactive oxygen species, proteases, and other potentially harmful effector molecules. Overall, there is a clear evidence for both helpful and harmful roles of neutrophils in HIV acquisition and pathogenesis. Further study, particularly of tissue neutrophils, is needed to elucidate the kinetics, phenotype, and functionality of neutrophils in HIV infection to better understand this dichotomy.

Keywords

Neutrophils HIV mucosal dysfunction HIV infection Tissue damage Mucosal immunology HIV protection 

Notes

Compliance with Ethical Standards

Conflict of Interest

Tiffany Hensley-McBain and Nichole R. Klatt declare grants from National Institutes of Health.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Nathan C. Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol. 2006;6(3):173–82.  https://doi.org/10.1038/nri1785.CrossRefPubMedGoogle Scholar
  2. 2.
    Chang TL, Vargas J Jr, DelPortillo A, Klotman ME. Dual role of alpha-defensin-1 in anti-HIV-1 innate immunity. J Clin Invest. 2005;115(3):765–73.  https://doi.org/10.1172/JCI21948.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Wu Z, Cocchi F, Gentles D, Ericksen B, Lubkowski J, Devico A, et al. Human neutrophil alpha-defensin 4 inhibits HIV-1 infection in vitro. FEBS Lett. 2005;579(1):162–6.  https://doi.org/10.1016/j.febslet.2004.11.062.CrossRefPubMedGoogle Scholar
  4. 4.
    Klotman ME, Chang TL. Defensins in innate antiviral immunity. Nat Rev Immunol. 2006;6(6):447–56.  https://doi.org/10.1038/nri1860.CrossRefPubMedGoogle Scholar
  5. 5.
    Mackewicz CE, Yuan J, Tran P, Diaz L, Mack E, Selsted ME, et al. Alpha-Defensins can have anti-HIV activity but are not CD8 cell anti-HIV factors. AIDS. 2003;17(14):F23–32.  https://doi.org/10.1097/01.aids.0000088209.77946.21. CrossRefPubMedGoogle Scholar
  6. 6.
    Klebanoff SJ, Coombs RW. Viricidal effect of polymorphonuclear leukocytes on human immunodeficiency virus-1. Role of the myeloperoxidase system. J Clin Invest. 1992;89(6):2014–7.  https://doi.org/10.1172/JCI115810.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Baldwin GC, Fuller ND, Roberts RL, Ho DD, Golde DW. Granulocyte- and granulocyte-macrophage colony-stimulating factors enhance neutrophil cytotoxicity toward HIV-infected cells. Blood. 1989;74(5):1673–7.PubMedGoogle Scholar
  8. 8.
    Smalls-Mantey A, Connors M, Sattentau QJ. Comparative efficiency of HIV-1-infected T cell killing by NK cells, monocytes and neutrophils. PLoS One. 2013;8(9):e74858.  https://doi.org/10.1371/journal.pone.0074858.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Saitoh T, Komano J, Saitoh Y, Misawa T, Takahama M, Kozaki T, et al. Neutrophil extracellular traps mediate a host defense response to human immunodeficiency virus-1. Cell Host Microbe. 2012;12(1):109–16.  https://doi.org/10.1016/j.chom.2012.05.015.CrossRefPubMedGoogle Scholar
  10. 10.
    Ackerman ME, Mikhailova A, Brown EP, Dowell KG, Walker BD, Bailey-Kellogg C, et al. Polyfunctional HIV-specific antibody responses are associated with spontaneous HIV control. PLoS Pathog. 2016;12(1):e1005315.  https://doi.org/10.1371/journal.ppat.1005315.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Ramsuran V, Kulkarni H, He W, Mlisana K, Wright EJ, Werner L, et al. Duffy-null-associated low neutrophil counts influence HIV-1 susceptibility in high-risk South African black women. Clin Infect Dis. 2011;52(10):1248–56.  https://doi.org/10.1093/cid/cir119. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kourtis AP, Hudgens MG, Kayira D, Team BANS. Neutrophil count in African mothers and newborns and HIV transmission risk. N Engl J Med. 2012;367(23):2260–2.  https://doi.org/10.1056/NEJMc1202292. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Elbim C, Monceaux V, Mueller YM, Lewis MG, Francois S, Diop O, et al. Early divergence in neutrophil apoptosis between pathogenic and nonpathogenic simian immunodeficiency virus infections of nonhuman primates. J Immunol. 2008;181(12):8613–23.  https://doi.org/10.4049/jimmunol.181.12.8613.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    • Prodger JL, Gray RH, Shannon B, Shahabi K, Kong X, Grabowski K, et al. Chemokine levels in the penile coronal sulcus correlate with HIV-1 acquisition and are reduced by male circumcision in Rakai, Uganda. PLoS Pathog. 2016;12(11):e1006025.  https://doi.org/10.1371/journal.ppat.1006025. A randomized longitudinal trial of uncircumcised men found that HIV acquisition was associated with detectable IL-8 levels in the penile coronal sulcus at the visit prior to seroconversion. Authors also demononstrated that IL-8 levels associated with neutrophils and HIV target cells in the foreskin. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Levinson P, Kaul R, Kimani J, Ngugi E, Moses S, MacDonald KS, et al. Levels of innate immune factors in genital fluids: association of alpha defensins and LL-37 with genital infections and increased HIV acquisition. AIDS. 2009;23(3):309–17.  https://doi.org/10.1097/QAD.0b013e328321809c.CrossRefPubMedGoogle Scholar
  16. 16.
    • Masson L, Passmore JA, Liebenberg LJ, Werner L, Baxter C, Arnold KB, et al. Genital inflammation and the risk of HIV acquisition in women. Clin Infect Dis. 2015;61(2):260–9.  https://doi.org/10.1093/cid/civ298. A study assessing cytokines in CVL of women enrolled in the CAPRISA 004 microbicide trial found that IL-8 was among inflammatory cytokines increased in women who subsequently acquired HIV infection compared to women who remained uninfected. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Moore RD, Keruly JC, Chaisson RE. Neutropenia and bacterial infection in acquired immunodeficiency syndrome. Arch Intern Med. 1995;155(18):1965–70.  https://doi.org/10.1001/archinte.1995.00430180067008.CrossRefPubMedGoogle Scholar
  18. 18.
    Keiser P, Higgs E, Smith J. Neutropenia is associated with bacteremia in patients infected with the human immunodeficiency virus. Am J Med Sci. 1996;312(3):118–22.  https://doi.org/10.1016/S0002-9629(15)41775-6.CrossRefPubMedGoogle Scholar
  19. 19.
    Roilides E, Holmes A, Blake C, Pizzo PA, Walsh TJ. Impairment of neutrophil antifungal activity against hyphae of Aspergillus fumigatus in children infected with human immunodeficiency virus. J Infect Dis. 1993;167(4):905–11.  https://doi.org/10.1093/infdis/167.4.905.CrossRefPubMedGoogle Scholar
  20. 20.
    Somsouk M, Estes JD, Deleage C, Dunham RM, Albright R, Inadomi JM, et al. Gut epithelial barrier and systemic inflammation during chronic HIV infection. AIDS. 2015;29(1):43–51.  https://doi.org/10.1097/QAD.0000000000000511.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Estes JD, Harris LD, Klatt NR, Tabb B, Pittaluga S, Paiardini M, et al. Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. PLoS Pathog. 2010;6(8):e1001052.  https://doi.org/10.1371/journal.ppat.1001052.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Cloke T, Munder M, Taylor G, Muller I, Kropf P. Characterization of a novel population of low-density granulocytes associated with disease severity in HIV-1 infection. PLoS One. 2012;7(11):e48939.  https://doi.org/10.1371/journal.pone.0048939.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Bowers NL, Helton ES, Huijbregts RP, Goepfert PA, Heath SL, Hel Z. Immune suppression by neutrophils in HIV-1 infection: role of PD-L1/PD-1 pathway. PLoS Pathog. 2014;10(3):e1003993.  https://doi.org/10.1371/journal.ppat.1003993.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Hernandez JC, Giraldo DM, Paul S, Urcuqui-Inchima S. Involvement of neutrophil hyporesponse and the role of toll-like receptors in human immunodeficiency virus 1 protection. PLoS One. 2015;10(3):e0119844.  https://doi.org/10.1371/journal.pone.0119844.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Graham-Pole J, Davie M, Willoughby ML. Cryopreservation of human granulocytes in liquid nitrogen. J Clin Pathol. 1977;30(8):758–62.  https://doi.org/10.1136/jcp.30.8.758.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Flo RW, Naess A, Nilsen A, Harthug S, Solberg CO. A. Longitudinal study of phagocyte function in HIV-infected patients. AIDS. 1994;8(6):771–7.  https://doi.org/10.1097/00002030-199406000-00008.CrossRefPubMedGoogle Scholar
  27. 27.
    Elbim C, Prevot MH, Bouscarat F, Franzini E, Chollet-Martin S, Hakim J, et al. Polymorphonuclear neutrophils from human immunodeficiency virus-infected patients show enhanced activation, diminished fMLP-induced L-selectin shedding, and an impaired oxidative burst after cytokine priming. Blood. 1994;84(8):2759–66.PubMedGoogle Scholar
  28. 28.
    Lazzarin A, Uberti Foppa C, Galli M, Mantovani A, Poli G, Franzetti F, et al. Impairment of polymorphonuclear leucocyte function in patients with acquired immunodeficiency syndrome and with lymphadenopathy syndrome. Clin Exp Immunol. 1986;65(1):105–11.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Lawrence MB, Springer TA. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 1991;65(5):859–73.  https://doi.org/10.1016/0092-8674(91)90393-D.CrossRefPubMedGoogle Scholar
  30. 30.
    Kobayashi SD, Voyich JM, Burlak C, DeLeo FR. Neutrophils in the innate immune response. Arch Immunol Ther Exp. 2005;53(6):505–17.Google Scholar
  31. 31.
    Ronsholt FF, Ullum H, Katzenstein TL, Gerstoft J, Ostrowski SR. Persistent inflammation and endothelial activation in HIV-1 infected patients after 12 years of antiretroviral therapy. PLoS One. 2013;8(6):e65182.  https://doi.org/10.1371/journal.pone.0065182.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    de Gaetano Donati K, Rabagliati R, Iacoviello L, Cauda R. HIV infection, HAART, and endothelial adhesion molecules: current perspectives. Lancet Infect Dis. 2004;4(4):213–22.  https://doi.org/10.1016/S1473-3099(04)00971-5.CrossRefPubMedGoogle Scholar
  33. 33.
    Borregaard N, Cowland JB. Granules of the human neutrophilic polymorphonuclear leukocyte. Blood. 1997;89(10):3503–21.PubMedGoogle Scholar
  34. 34.
    Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013;13(3):159–75.  https://doi.org/10.1038/nri3399.CrossRefPubMedGoogle Scholar
  35. 35.
    Hager M, Cowland JB, Borregaard N. Neutrophil granules in health and disease. J Intern Med. 2010;268(1):25–34.  https://doi.org/10.1111/j.1365-2796.2010.02237.x. PubMedGoogle Scholar
  36. 36.
    Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303(5663):1532–5.  https://doi.org/10.1126/science.1092385.CrossRefPubMedGoogle Scholar
  37. 37.
    Kang D, Liu G, Lundstrom A, Gelius E, Steiner H. A peptidoglycan recognition protein in innate immunity conserved from insects to humans. Proc Natl Acad Sci U S A. 1998;95(17):10078–82.  https://doi.org/10.1073/pnas.95.17.10078.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Lu J, Teh C, Kishore U, Reid KB. Collectins and ficolins: sugar pattern recognition molecules of the mammalian innate immune system. Biochim Biophys Acta. 2002;1572(2–3):387–400.  https://doi.org/10.1016/S0304-4165(02)00320-3.CrossRefPubMedGoogle Scholar
  39. 39.
    Hayashi F, Means TK, Luster AD. Toll-like receptors stimulate human neutrophil function. Blood. 2003;102(7):2660–9.  https://doi.org/10.1182/blood-2003-04-1078.CrossRefPubMedGoogle Scholar
  40. 40.
    Kumar V, Sharma A. Neutrophils: Cinderella of innate immune system. Int Immunopharmacol. 2010;10(11):1325–34.  https://doi.org/10.1016/j.intimp.2010.08.012.CrossRefPubMedGoogle Scholar
  41. 41.
    Korkmaz B, Horwitz MS, Jenne DE, Gauthier F. Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human diseases. Pharmacol Rev. 2010;62(4):726–59.  https://doi.org/10.1124/pr.110.002733.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Chen GY, Nunez G. Sterile inflammation: sensing and reacting to damage. Nat Rev Immunol. 2010;10(12):826–37.  https://doi.org/10.1038/nri2873.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Barnado A, Crofford LJ, Oates JC. At the bedside: neutrophil extracellular traps (NETs) as targets for biomarkers and therapies in autoimmune diseases. J Leukoc Biol. 2016;99(2):265–78.  https://doi.org/10.1189/jlb.5BT0615-234R.CrossRefPubMedGoogle Scholar
  44. 44.
    Shi X, Sims MD, Hanna MM, Xie M, Gulick PG, Zheng YH, et al. Neutropenia during HIV infection: adverse consequences and remedies. Int Rev Immunol. 2014;33(6):511–36.  https://doi.org/10.3109/08830185.2014.893301.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Levine AM, Karim R, Mack W, Gravink DJ, Anastos K, Young M, et al. Neutropenia in human immunodeficiency virus infection: data from the women’s interagency HIV study. Arch Intern Med. 2006;166(4):405–10.  https://doi.org/10.1001/archinte.166.4.405.PubMedGoogle Scholar
  46. 46.
    Carter CC, Onafuwa-Nuga A, McNamara LA, Riddell J, Bixby D, Savona MR, et al. HIV-1 infects multipotent progenitor cells causing cell death and establishing latent cellular reservoirs. Nat Med. 2010;16(4):446–51.  https://doi.org/10.1038/nm.2109.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Banda NK, Tomczak JA, Shpall EJ, Sipple J, Akkina RK, Steimer KS, et al. HIV-gp120 induced cell death in hematopoietic progenitor CD34+ cells. Apoptosis : Int J Program Cell Death. 1997;2(1):61–8.  https://doi.org/10.1023/A:1026439726053.CrossRefGoogle Scholar
  48. 48.
    Calenda V, Graber P, Delamarter JF, Chermann JC. Involvement of HIV nef protein in abnormal hematopoiesis in AIDS: in vitro study on bone marrow progenitor cells. Eur J Haematol. 1994;52(2):103–7.CrossRefPubMedGoogle Scholar
  49. 49.
    Rameshwar P, Denny TN, Gascon P. Enhanced HIV-1 activity in bone marrow can lead to myelopoietic suppression partially contributed by gag p24. J Immunol. 1996;157(9):4244–50.PubMedGoogle Scholar
  50. 50.
    Bahner I, Kearns K, Coutinho S, Leonard EH, Kohn DB. Infection of human marrow stroma by human immunodeficiency virus-1 (HIV-1) is both required and sufficient for HIV-1-induced hematopoietic suppression in vitro: demonstration by gene modification of primary human stroma. Blood. 1997;90(5):1787–98.PubMedGoogle Scholar
  51. 51.
    Moses AV, Williams S, Heneveld ML, Strussenberg J, Rarick M, Loveless M, et al. Human immunodeficiency virus infection of bone marrow endothelium reduces induction of stromal hematopoietic growth factors. Blood. 1996;87(3):919–25.PubMedGoogle Scholar
  52. 52.
    Re MC, Zauli G, Furlini G, Giovannini M, Ranieri S, Ramazzotti E, et al. GM-CSF production by CD4+ T-lymphocytes is selectively impaired during the course of HIV-1 infection. A possible indication of a preferential lesion of a specific subset of peripheral blood CD4+ T-lymphocytes. Microbiologica. 1992;15(3):265–70.PubMedGoogle Scholar
  53. 53.
    Bagnara GP, Zauli G, Re MC, Furlini G, Giovannini M, Ranieri S, et al. Impaired GM-CSF production by cultured light density mononuclear cells and T lymphocytes correlates with the number of circulating CFU-gm in HIV-1 seropositive subjects. Int J Cell Cloning. 1991;9(3):239–50.  https://doi.org/10.1002/stem.5530090308.CrossRefPubMedGoogle Scholar
  54. 54.
    Rubinstein DB, Farrington GK, O'Donnell C, Hartman KR, Wright DG. Autoantibodies to leukocyte alphaMbeta2 integrin glycoproteins in HIV infection. Clin Immunol. 1999;90(3):352–9.  https://doi.org/10.1006/clim.1998.4668.CrossRefPubMedGoogle Scholar
  55. 55.
    Ribera E, Ocana I, Almirante B, Gomez J, Monreal P, Martinez Vazquez JM. Autoimmune neutropenia and thrombocytopenia associated with development of antibodies to human immunodeficiency virus. J Infect. 1989;18(2):167–70.  https://doi.org/10.1016/S0163-4453(89)91206-1.CrossRefPubMedGoogle Scholar
  56. 56.
    Pitrak DL, Tsai HC, Mullane KM, Sutton SH, Stevens P. Accelerated neutrophil apoptosis in the acquired immunodeficiency syndrome. J Clin Invest. 1996;98(12):2714–9.  https://doi.org/10.1172/JCI119096. CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Elbim C, Monceaux V, Francois S, Hurtrel B, Gougerot-Pocidalo MA, Estaquier J. Increased neutrophil apoptosis in chronically SIV-infected macaques. Retrovirology. 2009;6(1):29.  https://doi.org/10.1186/1742-4690-6-29.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Campillo-Gimenez L, Casulli S, Dudoit Y, Seang S, Carcelain G, Lambert-Niclot S, et al. Neutrophils in antiretroviral therapy-controlled HIV demonstrate hyperactivation associated with a specific IL-17/IL-22 environment. J Allergy Clin Immunol. 2014;134(5):1142–52 e5.  https://doi.org/10.1016/j.jaci.2014.05.040.CrossRefPubMedGoogle Scholar
  59. 59.
    Roilides E, Mertins S, Eddy J, Walsh TJ, Pizzo PA, Rubin M. Impairment of neutrophil chemotactic and bactericidal function in children infected with human immunodeficiency virus type 1 and partial reversal after in vitro exposure to granulocyte-macrophage colony-stimulating factor. J Pediatr. 1990;117(4):531–40.  https://doi.org/10.1016/S0022-3476(05)80684-5.CrossRefPubMedGoogle Scholar
  60. 60.
    Ellis M, Gupta S, Galant S, Hakim S, VandeVen C, Toy C, et al. Impaired neutrophil function in patients with AIDS or AIDS-related complex: a comprehensive evaluation. J Infect Dis. 1988;158(6):1268–76.  https://doi.org/10.1093/infdis/158.6.1268.CrossRefPubMedGoogle Scholar
  61. 61.
    Dobmeyer TS, Raffel B, Dobmeyer JM, Findhammer S, Klein SA, Kabelitz D, et al. Decreased function of monocytes and granulocytes during HIV-1 infection correlates with CD4 cell counts. Eur J Med Res. 1995;1(1):9–15.PubMedGoogle Scholar
  62. 62.
    Kuritzkes DR, Parenti D, Ward DJ, Rachlis A, Wong RJ, Mallon KP, et al. Filgrastim prevents severe neutropenia and reduces infective morbidity in patients with advanced HIV infection: results of a randomized, multicenter, controlled trial. G-CSF 930101 Study Group. AIDS. 1998;12(1):65–74.  https://doi.org/10.1097/00002030-199801000-00008.CrossRefPubMedGoogle Scholar
  63. 63.
    Roilides E, Walsh TJ, Pizzo PA, Rubin M. Granulocyte colony-stimulating factor enhances the phagocytic and bactericidal activity of normal and defective human neutrophils. J Infect Dis. 1991;163(3):579–83.  https://doi.org/10.1093/infdis/163.3.579.CrossRefPubMedGoogle Scholar
  64. 64.
    Coffey MJ, Phare SM, George S, Peters-Golden M, Kazanjian PH. Granulocyte colony-stimulating factor administration to HIV-infected subjects augments reduced leukotriene synthesis and anticryptococcal activity in neutrophils. J Clin Invest. 1998;102(4):663–70.  https://doi.org/10.1172/JCI2117. CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Mastroianni CM, Lichtner M, Mengoni F, D'Agostino C, Forcina G, d'Ettorre G, et al. Improvement in neutrophil and monocyte function during highly active antiretroviral treatment of HIV-1-infected patients. AIDS. 1999;13(8):883–90.  https://doi.org/10.1097/00002030-199905280-00003.CrossRefPubMedGoogle Scholar
  66. 66.
    Mastroianni CM, d'Ettorre G, Forcina G, Lichtner M, Mengoni F, D'Agostino C, et al. Interleukin-15 enhances neutrophil functional activity in patients with human immunodeficiency virus infection. Blood. 2000;96(5):1979–84.PubMedGoogle Scholar
  67. 67.
    Roilides E, Venzon D, Pizzo PA, Rubin M. Effects of antiretroviral dideoxynucleosides on polymorphonuclear leukocyte function. Antimicrob Agents Chemother. 1990;34(9):1672–7.  https://doi.org/10.1128/AAC.34.9.1672.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Hadad N, Levy R, Schlaeffer F, Riesenberg K. Direct effect of human immunodeficiency virus protease inhibitors on neutrophil function and apoptosis via calpain inhibition. Clin Vaccine Immunol: CVI. 2007;14(11):1515–21.  https://doi.org/10.1128/CVI.00130-07. CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Deeks SG, Lewin SR, Havlir DV. The end of AIDS: HIV infection as a chronic disease. Lancet. 2013;382(9903):1525–33.  https://doi.org/10.1016/S0140-6736(13)61809-7.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Burgener A, McGowan I, Klatt NR. HIV and mucosal barrier interactions: consequences for transmission and pathogenesis. Curr Opin Immunol. 2015;36:22–30.  https://doi.org/10.1016/j.coi.2015.06.004.CrossRefPubMedGoogle Scholar
  71. 71.
    Batman PA, Miller AR, Forster SM, Harris JR, Pinching AJ, Griffin GE. Jejunal enteropathy associated with human immunodeficiency virus infection: quantitative histology. J Clin Pathol. 1989;42(3):275–81.  https://doi.org/10.1136/jcp.42.3.275.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Brenchley JM, Douek DC. HIV infection and the gastrointestinal immune system. Mucosal Immunol. 2008;1(1):23–30.  https://doi.org/10.1038/mi.2007.1.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Sandler NG, Douek DC. Microbial translocation in HIV infection: causes, consequences and treatment opportunities. Nat Rev Microbiol. 2012;10(9):655–66.  https://doi.org/10.1038/nrmicro2848.CrossRefPubMedGoogle Scholar
  74. 74.
    Sankaran S, George MD, Reay E, Guadalupe M, Flamm J, Prindiville T, et al. Rapid onset of intestinal epithelial barrier dysfunction in primary human immunodeficiency virus infection is driven by an imbalance between immune response and mucosal repair and regeneration. J Virol. 2008;82(1):538–45.  https://doi.org/10.1128/JVI.01449-07.CrossRefPubMedGoogle Scholar
  75. 75.
    Nazli A, Chan O, Dobson-Belaire WN, Ouellet M, Tremblay MJ, Gray-Owen SD, et al. Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation. PLoS Pathog. 2010;6(4):e1000852.  https://doi.org/10.1371/journal.ppat.1000852.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Buccigrossi V, Laudiero G, Nicastro E, Miele E, Esposito F, Guarino A. The HIV-1 transactivator factor (Tat) induces enterocyte apoptosis through a redox-mediated mechanism. PLoS One. 2011;6(12):e29436.  https://doi.org/10.1371/journal.pone.0029436.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Canani RB, Cirillo P, Mallardo G, Buccigrossi V, Secondo A, Annunziato L, et al. Effects of HIV-1 Tat protein on ion secretion and on cell proliferation in human intestinal epithelial cells. Gastroenterology. 2003;124(2):368–76.  https://doi.org/10.1053/gast.2003.50056.CrossRefPubMedGoogle Scholar
  78. 78.
    Schmitz H, Rokos K, Florian P, Gitter AH, Fromm M, Scholz P, et al. Supernatants of HIV-infected immune cells affect the barrier function of human HT-29/B6 intestinal epithelial cells. AIDS. 2002;16(7):983–91.  https://doi.org/10.1097/00002030-200205030-00004.CrossRefPubMedGoogle Scholar
  79. 79.
    Veazey RS, DeMaria M, Chalifoux LV, Shvetz DE, Pauley DR, Knight HL, et al. Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science. 1998;280(5362):427–31.  https://doi.org/10.1126/science.280.5362.427.CrossRefPubMedGoogle Scholar
  80. 80.
    Klatt NR, Estes JD, Sun X, Ortiz AM, Barber JS, Harris LD, et al. Loss of mucosal CD103+ DCs and IL-17+ and IL-22+ lymphocytes is associated with mucosal damage in SIV infection. Mucosal Immunol. 2012;5(6):646–57.  https://doi.org/10.1038/mi.2012.38.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Klatt NR, Funderburg NT, Brenchley JM. Microbial translocation, immune activation, and HIV disease. Trends Microbiol. 2013;21(1):6–13.  https://doi.org/10.1016/j.tim.2012.09.001.CrossRefPubMedGoogle Scholar
  82. 82.
    Klatt NR, Chomont N, Douek DC, Deeks SG. Immune activation and HIV persistence: implications for curative approaches to HIV infection. Immunol Rev. 2013;254(1):326–42.  https://doi.org/10.1111/imr.12065.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12(12):1365–71.  https://doi.org/10.1038/nm1511.CrossRefPubMedGoogle Scholar
  84. 84.
    Lichtfuss GF, Hoy J, Rajasuriar R, Kramski M, Crowe SM, Lewin SR. Biomarkers of immune dysfunction following combination antiretroviral therapy for HIV infection. Biomark Med. 2011;5(2):171–86.  https://doi.org/10.2217/bmm.11.15.CrossRefPubMedGoogle Scholar
  85. 85.
    Sandler NG, Wand H, Roque A, Law M, Nason MC, Nixon DE, et al. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis. 2011;203(6):780–90.  https://doi.org/10.1093/infdis/jiq118.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Rodger AJ, Fox Z, Lundgren JD, Kuller LH, Boesecke C, Gey D, et al. Activation and coagulation biomarkers are independent predictors of the development of opportunistic disease in patients with HIV infection. J Infect Dis. 2009;200(6):973–83.  https://doi.org/10.1086/605447.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008;5(10):e203.  https://doi.org/10.1371/journal.pmed.0050203.CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Natsui M, Kawasaki K, Takizawa H, Hayashi SI, Matsuda Y, Sugimura K, et al. Selective depletion of neutrophils by a monoclonal antibody, RP-3, suppresses dextran sulphate sodium-induced colitis in rats. J Gastroenterol Hepatol. 1997;12(12):801–8.  https://doi.org/10.1111/j.1440-1746.1997.tb00375.x.CrossRefPubMedGoogle Scholar
  89. 89.
    Bressenot A, Salleron J, Bastien C, Danese S, Boulagnon-Rombi C, Peyrin-Biroulet L. Comparing histological activity indexes in UC. Gut. 2015;64(9):1412–8.  https://doi.org/10.1136/gutjnl-2014-307477.CrossRefPubMedGoogle Scholar
  90. 90.
    Kuhl AA, Kakirman H, Janotta M, Dreher S, Cremer P, Pawlowski NN, et al. Aggravation of different types of experimental colitis by depletion or adhesion blockade of neutrophils. Gastroenterology. 2007;133(6):1882–92.  https://doi.org/10.1053/j.gastro.2007.08.073.CrossRefPubMedGoogle Scholar
  91. 91.
    Nemoto Y, Kanai T, Tohda S, Totsuka T, Okamoto R, Tsuchiya K, et al. Negative feedback regulation of colitogenic CD4+ T cells by increased granulopoiesis. Inflamm Bowel Dis. 2008;14(11):1491–503.  https://doi.org/10.1002/ibd.20531.CrossRefPubMedGoogle Scholar
  92. 92.
    Zhang R, Ito S, Nishio N, Cheng Z, Suzuki H, Isobe K. Up-regulation of Gr1+CD11b+ population in spleen of dextran sulfate sodium administered mice works to repair colitis. Inflamm Allergy Drug Targets. 2011;10(1):39–46.  https://doi.org/10.2174/187152811794352114.CrossRefPubMedGoogle Scholar
  93. 93.
    Nash S, Stafford J, Madara JL. Effects of polymorphonuclear leukocyte transmigration on the barrier function of cultured intestinal epithelial monolayers. J Clin Invest. 1987;80(4):1104–13.  https://doi.org/10.1172/JCI113167. CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Nusrat A, Parkos CA, Liang TW, Carnes DK, Madara JL. Neutrophil migration across model intestinal epithelia: monolayer disruption and subsequent events in epithelial repair. Gastroenterology. 1997;113(5):1489–500.  https://doi.org/10.1053/gast.1997.v113.pm9352851.CrossRefPubMedGoogle Scholar
  95. 95.
    Kucharzik T, Walsh SV, Chen J, Parkos CA, Nusrat A. Neutrophil transmigration in inflammatory bowel disease is associated with differential expression of epithelial intercellular junction proteins. Am J Pathol. 2001;159(6):2001–9.  https://doi.org/10.1016/S0002-9440(10)63051-9.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Pillay J, Tak T, Kamp VM, Koenderman L. Immune suppression by neutrophils and granulocytic myeloid-derived suppressor cells: similarities and differences. Cell Mol life Sci: CMLS. 2013;70(20):3813–27.  https://doi.org/10.1007/s00018-013-1286-4. CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Prodger JL, Hirbod T, Kigozi G, Nalugoda F, Reynolds SJ, Galiwango R, et al. Immune correlates of HIV exposure without infection in foreskins of men from Rakai, Uganda. Mucosal Immunol. 2014;7(3):634–44.  https://doi.org/10.1038/mi.2013.83.CrossRefPubMedGoogle Scholar
  98. 98.
    Sips M, Krykbaeva M, Diefenbach TJ, Ghebremichael M, Bowman BA, Dugast AS, et al. Fc receptor-mediated phagocytosis in tissues as a potent mechanism for preventive and therapeutic HIV vaccine strategies. Mucosal Immunol. 2016;9(6):1584–95.  https://doi.org/10.1038/mi.2016.12.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Gursoy UK, Kononen E, Luukkonen N, Uitto VJ. Human neutrophil defensins and their effect on epithelial cells. J Periodontol. 2013;84(1):126–33.  https://doi.org/10.1902/jop.2012.120017.CrossRefPubMedGoogle Scholar
  100. 100.
    Arnold KB, Burgener A, Birse K, Romas L, Dunphy LJ, Shahabi K, et al. Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells. Mucosal Immunol. 2016;9(1):194–205.  https://doi.org/10.1038/mi.2015.51.CrossRefPubMedGoogle Scholar
  101. 101.
    Pelletier M, Maggi L, Micheletti A, Lazzeri E, Tamassia N, Costantini C, et al. Evidence for a cross-talk between human neutrophils and Th17 cells. Blood. 2010;115(2):335–43.  https://doi.org/10.1182/blood-2009-04-216085.CrossRefPubMedGoogle Scholar
  102. 102.
    Lin L, Ibrahim AS, Xu X, Farber JM, Avanesian V, Baquir B, et al. Th1-Th17 cells mediate protective adaptive immunity against Staphylococcus aureus and Candida albicans infection in mice. PLoS Pathog. 2009;5(12):e1000703.  https://doi.org/10.1371/journal.ppat.1000703.CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Khader SA, Gaffen SL, Kolls JK. Th17 cells at the crossroads of innate and adaptive immunity against infectious diseases at the mucosa. Mucosal Immunol. 2009;2(5):403–11.  https://doi.org/10.1038/mi.2009.100.CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Rodriguez-Garcia M, Barr FD, Crist SG, Fahey JV, Wira CR. Phenotype and susceptibility to HIV infection of CD4+ Th17 cells in the human female reproductive tract. Mucosal Immunol. 2014;7(6):1375–85.  https://doi.org/10.1038/mi.2014.26.CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    • Stieh DJ, Matias E, Xu H, Fought AJ, Blanchard JL, Marx PA, et al. Th17 cells are preferentially infected very early after vaginal transmission of SIV in macaques. Cell Host Microbe. 2016;19(4):529–40.  https://doi.org/10.1016/j.chom.2016.03.005. A study assessing the phenotype of cells found in distinct foci of infection early after vaginal inoculation of rhesus macaques with SIV found that CCR6+ TH17 cells are primary targets during vaginal transmission. CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PharmaceuticsUniversity of WashingtonSeattleUSA
  2. 2.Washington National Primate Research Center (WaNPRC)University of WashingtonSeattleUSA

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