Proliferative capacity and cytokine production by cells of HIV-infected and uninfected adults with different helminth infection phenotypes in South Africa.

Zilungile L Mkhize-Kwitshana,Gerhard Walzl,Musawenkosi Lh Mabaso

doi:10.1186/1471-2334-14-499

Zilungile L Mkhize-Kwitshana, Gerhard Walzl + Show 1 more

Open Access

https://doi.org/10.1186/1471-2334-14-499

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Abstract

BackgroundIt has been suggested that the proliferative capacity of cells from individuals with HIV or both HIV and helminth infections is attenuated and cytokine production is dysregulated. This study describes peripheral blood mononuclear cell proliferation capacity and cytokine profile from individuals with HIV or both HIV and helminth infections in South Africa.MethodsForty HIV-infected and 22 HIV-uninfected participants were randomly selected and stratified into different helminth infection phenotypes by egg excretion and Ascaris lumbricoides specific –immunoglobulin-E (IgE) levels. Five day cell cultures of participants, unstimulated or stimulated with Phytohaemaglutinnin, Streptokinase, HIV-1 p24 and Ascaris lumbricoides worm antigens were stained with monoclonal antibody-fluorochrome conjugates (Ki67-FITC and CTLA-APC-4). Percentage expression of Ki67 and CTLA-4 was measured to determine cell proliferation and regulation, respectively. Culture supernatants were analysed for the expression of 13 cytokines using the Bioplex (BioRad) system. Kruskal Wallis was used to test for differences in variables between helminth infected subgroups who were either having eggs in stool and high IgE (egg+IgEhi); or eggs in stool and low IgE (egg+IgElo); or no eggs in stool and high IgE (egg-IgEhi) and those without helminth infection (egg-IgElo).ResultsIndividuals excreting eggs in stool with high serum IgE (egg+IgEhi phenotype) had potent mitogen responses but consistently produced low, but statistically non-significant antigen–specific (HIV-1 p24 (p = 0.41) and Ascaris (p = 0.19) and recall antigen (Streptokinase; p = 0.31) Ki67 responses. The group also had reduced type 1 cytokines. Individuals excreting eggs in stool with low serum IgE( egg+IgElo phenotype) had a more favourable antiviral profile, characterized by higher IFNγ, IL-2, lower IL-4 and higher IL-10 production.ConclusionThe findings suggest that dual HIV/helminth infection with egg excretion and/or high Ascaris IgE phenotye may be linked with poor proliferative capacity and deleterious cytokine profile with regards to HIV control.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-499) contains supplementary material, which is available to authorized users.

Highlights

It has been suggested that the proliferative capacity of cells from individuals with HIV or both HIV and helminth infections is attenuated and cytokine production is dysregulated
The present study further describes peripheral blood mononuclear cell proliferation capacity as measured by Ki67 expression, as well as cytokine profiles in the same HIV-infected and negative South African adults with different helminth infection phenotypes in order to determine if cells from dually infected individuals have skewed cytokine production and more impaired capacity to proliferate in response to antigen stimulation
The CD4+ cell levels in this subgroup were similar to the subgroup without evidence of helminth infection and in both cases were above 0.2 cells/ml and lower than the other two subgroups

Summary

Introduction

It has been suggested that the proliferative capacity of cells from individuals with HIV or both HIV and helminth infections is attenuated and cytokine production is dysregulated. HIV receptor molecules (CCR5, CXC-R4 and CD4), eosinophilia, induction of persistent immune activation and anergy are some of the immune modulatory factors by which helminths are suggested to promote HIV infection and disease progression [1,3] Both HIV and helminth infection are characterized by chronic immune activation and dysregulation of immune responses to pathogens typified by impaired capacity of immune cells to proliferate in response to antigenic stimulus [1,4]. It is expected that dual infection would have an additive effect on the immune defects associated with the individual infections It is noted, that despite attempts to derive scientifically conclusive evidence of a positive impact of deworming on HIV progression, studies have, in the main, reported conflicting results [7]. The aim is to further define immunological effects associated with helminth infection in the context of HIV progression parameters in order to extend this body of knowledge

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