Alterations of the NK cell pool in HIV/HCV co-infection

PLoS One. 2017 Apr 5;12(4):e0174465. doi: 10.1371/journal.pone.0174465. eCollection 2017.

Abstract

Background: A relevant proportion of human immunodeficiency virus (HIV) infected patients is co-infected with the hepatitis C virus (HCV). HCV co-infection in HIV-positive patients is associated with faster progression of liver disease in comparison to HCV mono-infection. Natural killer (NK) cells critically modulate the natural course of HCV infection. Both HIV and HCV mono-infection are associated with alterations of the NK cell pool. However, little data is available concerning phenotype and function of NK cells in HIV/HCV co-infection.

Methods: A total of 34 HIV/HCV co-infected, 35 HIV and 39 HCV mono-infected patients and 43 healthy control persons were enrolled into this study. All HIV-positive patients were under effective antiretroviral therapy. NK cell phenotype, IFN-γ production and degranulation were studied by flow cytometry.

Results: NK cell frequency in HIV/HCV co-infection was significantly lower than in healthy individuals but did not differ from HIV and HCV mono-infection. HIV/HCV co-infection was associated with significantly decreased expression of the maturation/differentiation markers CD27/62L/127 on NK cells but increased expression of CD57 compared to healthy controls. Of note, expression also differed significantly from HCV mono-infection but was similar to HIV mono-infection, suggesting a pronounced impact of HIV on these alterations. Similar findings were made with regard to the NK cell receptors NKG2A/C and NKp30. More importantly, NK cells in co-infection displayed a highly impaired functional activity with significantly lower IFN-γ production and degranulation than in healthy donors as well as HIV and HCV mono-infection, suggesting a synergistic effect of both viruses.

Conclusions: Our data indicate that HIV/HCV co-infection is associated with significant alterations of the NK cell pool, which might be involved in the rapid progression of liver disease in co-infected patients and which mainly reflect alterations observed in HIV mono-infection.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Coinfection / immunology*
  • Coinfection / virology
  • Cross-Sectional Studies
  • Flow Cytometry
  • HIV Infections / complications*
  • HIV Infections / immunology
  • Hepatitis C / complications*
  • Hepatitis C / immunology
  • Humans
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / physiology*
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Interferon-gamma

Grants and funding

This work was supported by a BONFOR grant (O-107.0116 [DK]), the German Research Foundation (DFG SFB/TR 57 [US, JN], DFG KR4521/1-1 [BK], the H. W. and J. Hector Foundation (grant number M69 [JN]) and the German Center for Infection Research (DZIF TTU 04.810 [JN]).