Limits...
Increased CD56(bright) NK cells in HIV-HCV co-infection and HCV mono-infection are associated with distinctive alterations of their phenotype.

Bhardwaj S, Ahmad F, Wedemeyer H, Cornberg M, Schulze Zur Wiesch J, van Lunzen J, Sarin SK, Schmidt RE, Meyer-Olson D - Virol. J. (2016)

Bottom Line: HIV-HCV co-infection is associated with accelerated progression to hepatic fibrosis, cirrhosis and hepatocellular carcinoma than HCV mono-infection.The expression of NKp46 in HIV-HCV co-infected group was significantly upregulated as compared to both HIV as well as HCV mono-infections while NKp30 expression in the HIV-HCV co-infected group significantly differed as compared to HIV mono-infection.HCV mono-infection has a dominant effect on NKp30 expression while NKG2D and CD127 expressions remained same in all the groups.

View Article: PubMed Central - PubMed

Affiliation: Institute of Liver and Billiary Sciences, New Delhi, India.

ABSTRACT

Background: HIV-HCV co-infection is associated with accelerated progression to hepatic fibrosis, cirrhosis and hepatocellular carcinoma than HCV mono-infection. The contribution of innate immunity during HIV-HCV co-infection has been a relatively under-investigated area. Natural killer (NK) cells are pivotal sentinels of innate immunity against viruses and tumour cells. In this study we evaluated the effect of HIV-HCV co-infection on peripheral blood NK cell subsets with emphasis on the phenotype of CD56(bright) NK cells.

Methods: Sixty patients were included in the study; HIV mono-infected (n = 12), HCV mono-infected (n = 15), HCV-HIV co-infected (n = 21) and healthy controls (n = 16). PBMCs were isolated and immunophenotyping of NK cells was performed by flowcytometry.

Results: We observed an expansion of CD56(bright) NK cell subset in HIV-HCV co-infection as compared to healthy controls and HIV mono-infected group. All the infected groups had an upregulated expression of the activating receptor NKG2D on CD56(bright) NK cells in comparison to healthy controls while not differing amongst themselves. The expression of NKp46 in HIV-HCV co-infected group was significantly upregulated as compared to both HIV as well as HCV mono-infections while NKp30 expression in the HIV-HCV co-infected group significantly differed as compared to HIV mono-infection. The CD56(bright) NK cell subset was activated in HIV-HCV co-infection as assessed by the expression of CD69 as compared to healthy controls but was significantly downregulated in comparison to HIV mono-infection. CD95 expression on CD56(bright) NK cells followed the same pattern where there was an increased expression of CD95 in HIV mono-infection and HIV-HCV co-infection as compared to healthy controls. In contrast to CD69 expression, CD95 expression in HCV mono-infection was decreased when compared to HIV mono-infection and HIV-HCV co-infection. Finally, expression of CXCR3 on CD56(bright) NK cells was increased in HIV-HCV co-infection in comparison to HIV mono-infection while remaining similar to HCV mono-infection.

Conclusion: Thus, HIV-HCV co-infection is able to modulate the phenotype of CD56(bright) NK cell subset in a unique way such that NKp46 and CXCR3 expressions are distinct for co-infection while both mono-infections have an additive effect on CD56(bright), CD69 with CD95 expressions. HCV mono-infection has a dominant effect on NKp30 expression while NKG2D and CD127 expressions remained same in all the groups.

No MeSH data available.


Related in: MedlinePlus

Increased CD56brightCD16+/- NK cells in HIV-HCV co-infection. a Representative gating scheme for identification of CD56brightCD16+/- NK cells. b Comparison of percentage of the CD56bright NK cell subpopulation in control subjects (n = 13), HIV seropositive (n = 12), HIV-HCV co-infected (n = 21) and HCV mono-infected individuals (n = 15) on CD56bright CD16+/− NK cells. (c) Comparison of log percentage of the CD56bright NK cells expressing CD16 in control subjects (n = 13), HIV seropositive (n = 12), HIV-HCV co-infected (n = 21) and HCV mono-infected individuals (n = 15) on CD56+CD16+/- NK cells. *, P < 0.05; ns - not significant (P > 0.05). In the dot plot figure horizontal line represents % Mean ± SEM and Log % Mean ± SEM respectively
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4835889&req=5

Fig1: Increased CD56brightCD16+/- NK cells in HIV-HCV co-infection. a Representative gating scheme for identification of CD56brightCD16+/- NK cells. b Comparison of percentage of the CD56bright NK cell subpopulation in control subjects (n = 13), HIV seropositive (n = 12), HIV-HCV co-infected (n = 21) and HCV mono-infected individuals (n = 15) on CD56bright CD16+/− NK cells. (c) Comparison of log percentage of the CD56bright NK cells expressing CD16 in control subjects (n = 13), HIV seropositive (n = 12), HIV-HCV co-infected (n = 21) and HCV mono-infected individuals (n = 15) on CD56+CD16+/- NK cells. *, P < 0.05; ns - not significant (P > 0.05). In the dot plot figure horizontal line represents % Mean ± SEM and Log % Mean ± SEM respectively

Mentions: We defined NK cells as CD3−CD14−CD19− lymphocytes expressing either CD16 or CD56 or both as described previously [10]. Utilizing CD56 and CD16 we defined CD56bright NK cell population in peripheral blood as shown in Fig. 1a. The percentage of CD56brightCD16+/− NK cells in HIV and HCV mono-infections did not differ significantly as compared to the healthy controls. On the other hand HIV-HCV co-infection had significant upregulation of CD56brightCD16+/− NK cells as compared to healthy controls. As compared to mono-infections HIV-HCV co-infection had an upregulated expression of CD56brightCD16+/− NK cells than HIV mono-infection only. Although HCV mono-infection showed a trend towards increased CD56brightCD16+/− NK cells, only HIV-HCV co-infection resulted in an increase that was significantly different from both healthy controls and HIV mono-infection (Fig. 1b). The log percentage of CD56bright NK cells expressing CD16 in HIV-HCV co-infected patients also differed significantly as compared to healthy controls and HIV mono-infected group (Fig. 1c).Fig. 1


Increased CD56(bright) NK cells in HIV-HCV co-infection and HCV mono-infection are associated with distinctive alterations of their phenotype.

Bhardwaj S, Ahmad F, Wedemeyer H, Cornberg M, Schulze Zur Wiesch J, van Lunzen J, Sarin SK, Schmidt RE, Meyer-Olson D - Virol. J. (2016)

Increased CD56brightCD16+/- NK cells in HIV-HCV co-infection. a Representative gating scheme for identification of CD56brightCD16+/- NK cells. b Comparison of percentage of the CD56bright NK cell subpopulation in control subjects (n = 13), HIV seropositive (n = 12), HIV-HCV co-infected (n = 21) and HCV mono-infected individuals (n = 15) on CD56bright CD16+/− NK cells. (c) Comparison of log percentage of the CD56bright NK cells expressing CD16 in control subjects (n = 13), HIV seropositive (n = 12), HIV-HCV co-infected (n = 21) and HCV mono-infected individuals (n = 15) on CD56+CD16+/- NK cells. *, P < 0.05; ns - not significant (P > 0.05). In the dot plot figure horizontal line represents % Mean ± SEM and Log % Mean ± SEM respectively
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835889&req=5

Fig1: Increased CD56brightCD16+/- NK cells in HIV-HCV co-infection. a Representative gating scheme for identification of CD56brightCD16+/- NK cells. b Comparison of percentage of the CD56bright NK cell subpopulation in control subjects (n = 13), HIV seropositive (n = 12), HIV-HCV co-infected (n = 21) and HCV mono-infected individuals (n = 15) on CD56bright CD16+/− NK cells. (c) Comparison of log percentage of the CD56bright NK cells expressing CD16 in control subjects (n = 13), HIV seropositive (n = 12), HIV-HCV co-infected (n = 21) and HCV mono-infected individuals (n = 15) on CD56+CD16+/- NK cells. *, P < 0.05; ns - not significant (P > 0.05). In the dot plot figure horizontal line represents % Mean ± SEM and Log % Mean ± SEM respectively
Mentions: We defined NK cells as CD3−CD14−CD19− lymphocytes expressing either CD16 or CD56 or both as described previously [10]. Utilizing CD56 and CD16 we defined CD56bright NK cell population in peripheral blood as shown in Fig. 1a. The percentage of CD56brightCD16+/− NK cells in HIV and HCV mono-infections did not differ significantly as compared to the healthy controls. On the other hand HIV-HCV co-infection had significant upregulation of CD56brightCD16+/− NK cells as compared to healthy controls. As compared to mono-infections HIV-HCV co-infection had an upregulated expression of CD56brightCD16+/− NK cells than HIV mono-infection only. Although HCV mono-infection showed a trend towards increased CD56brightCD16+/− NK cells, only HIV-HCV co-infection resulted in an increase that was significantly different from both healthy controls and HIV mono-infection (Fig. 1b). The log percentage of CD56bright NK cells expressing CD16 in HIV-HCV co-infected patients also differed significantly as compared to healthy controls and HIV mono-infected group (Fig. 1c).Fig. 1

Bottom Line: HIV-HCV co-infection is associated with accelerated progression to hepatic fibrosis, cirrhosis and hepatocellular carcinoma than HCV mono-infection.The expression of NKp46 in HIV-HCV co-infected group was significantly upregulated as compared to both HIV as well as HCV mono-infections while NKp30 expression in the HIV-HCV co-infected group significantly differed as compared to HIV mono-infection.HCV mono-infection has a dominant effect on NKp30 expression while NKG2D and CD127 expressions remained same in all the groups.

View Article: PubMed Central - PubMed

Affiliation: Institute of Liver and Billiary Sciences, New Delhi, India.

ABSTRACT

Background: HIV-HCV co-infection is associated with accelerated progression to hepatic fibrosis, cirrhosis and hepatocellular carcinoma than HCV mono-infection. The contribution of innate immunity during HIV-HCV co-infection has been a relatively under-investigated area. Natural killer (NK) cells are pivotal sentinels of innate immunity against viruses and tumour cells. In this study we evaluated the effect of HIV-HCV co-infection on peripheral blood NK cell subsets with emphasis on the phenotype of CD56(bright) NK cells.

Methods: Sixty patients were included in the study; HIV mono-infected (n = 12), HCV mono-infected (n = 15), HCV-HIV co-infected (n = 21) and healthy controls (n = 16). PBMCs were isolated and immunophenotyping of NK cells was performed by flowcytometry.

Results: We observed an expansion of CD56(bright) NK cell subset in HIV-HCV co-infection as compared to healthy controls and HIV mono-infected group. All the infected groups had an upregulated expression of the activating receptor NKG2D on CD56(bright) NK cells in comparison to healthy controls while not differing amongst themselves. The expression of NKp46 in HIV-HCV co-infected group was significantly upregulated as compared to both HIV as well as HCV mono-infections while NKp30 expression in the HIV-HCV co-infected group significantly differed as compared to HIV mono-infection. The CD56(bright) NK cell subset was activated in HIV-HCV co-infection as assessed by the expression of CD69 as compared to healthy controls but was significantly downregulated in comparison to HIV mono-infection. CD95 expression on CD56(bright) NK cells followed the same pattern where there was an increased expression of CD95 in HIV mono-infection and HIV-HCV co-infection as compared to healthy controls. In contrast to CD69 expression, CD95 expression in HCV mono-infection was decreased when compared to HIV mono-infection and HIV-HCV co-infection. Finally, expression of CXCR3 on CD56(bright) NK cells was increased in HIV-HCV co-infection in comparison to HIV mono-infection while remaining similar to HCV mono-infection.

Conclusion: Thus, HIV-HCV co-infection is able to modulate the phenotype of CD56(bright) NK cell subset in a unique way such that NKp46 and CXCR3 expressions are distinct for co-infection while both mono-infections have an additive effect on CD56(bright), CD69 with CD95 expressions. HCV mono-infection has a dominant effect on NKp30 expression while NKG2D and CD127 expressions remained same in all the groups.

No MeSH data available.


Related in: MedlinePlus