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

Abstract

BackgroundA 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.MethodsA 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.ResultsNK 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.ConclusionsOur 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.

Liver cirrhosis in HIV/HCV‐coinfected individuals is related to NK cell dysfunction and exhaustion, but not to an impaired NK cell modulation by CD4+ T‐cells

“…It is evident that experimental settings, for example, cytokine prestimulation of NK cells, evaluation of spontaneous degranulation, and interaction with other immune cells are critical when analysing ex vivo NK cell cytotoxicity. Together, our results are consistent with those reporting impaired functionality of NK cells during HCV monoinfection , and also HIV/HCV coinfection . However, they could be also interpreted in the context of a functional NK cell dichotomy, where NK cells display a decreased production of antiviral cytokines but an enhanced basal cytotoxicity, which is impaired when these cells are exposed to their targets .…”

“…Association between NK cell phenotype and function and the outcome of acute HCV infection was extensively reported , nevertheless, it remains unclear whether phenotypical and/or functional characteristics of NK cells are actually determinants for the rate of liver fibrosis progression. We and others have previously shown an association between low NK and CD4 + T‐cell counts with advanced liver fibrosis in HIV/HCV‐coinfected individuals . Here, we provide further support for this phenomenon, and also demonstrate that NK functionality is significantly impaired in coinfected individuals with advanced fibrosis.…”

“…NK cells have shown to play an important role in the immune response against HCV infection and in the modulation of liver fibrosis development. It was previously reported in HCV monoinfection and HIV/HCV coinfection that peripheral NK cell frequency is significantly decreased . Recently, we showed that among HIV/HCV‐coinfected subjects, advanced fibrosis was associated to the lowest frequencies of circulating NK cells .…”

Hepatitis C virus direct‐acting antivirals therapy impacts on extracellular vesicles microRNAs content and on their immunomodulating properties

“…The inhibition of degranulation observed in the functional assays was an unexpected result, as several studies report higher cytotoxic capacity in blood‐derived NK cells of HCV patients, mainly due to TRAIL upregulation. However, recent studies have reported a downregulation of CD107a and inhibition of degranulation of NK cells isolated from the blood of HCV and HCV/HIV coinfected patients after coincubation with HCV‐infected hepatocytes . Furthermore, Fugier and colleagues have shown that, in vivo, NK cell degranulation activity can be significantly impaired in patients with highest inflammation and fibrosis Metavir scores .…”

Direct-Acting Antivirals in Chronic Hepatitis C Infection with Liver Cirrhosis

“…Intravenous drug users may be at risk of both infections, and intravenous drug users represent the most common cause of new HCV infections [1]. Co-infection with HCV and HIV also appears to alter the host immune system, with strong evidence of decreased natural killer cells [45]. Clinicians also must exercise caution as there remains a possibility of drug-drug interaction, including hepatotoxicity between Highly Active-Antiretroviral Therapy (HAART) and DAA Direct-Acting Antivirals in Chronic Hepatitis C Infection with Liver Cirrhosis DOI: http://dx.doi.org/10.5772/intechopen.83609 [2].…”