A comparison of frequencies and function of myeloid derived suppressor cells (MDSCS) IN TB/HIV co-infected and HIV mono-infected individuals in Uganda

Abstract

Background Myeloid-derived suppressor cells (MDSC) encompass a subset of myeloid cells, which suppress both innate and adaptive immune functions. These cells negatively regulate the immune function either by arginine depletion, reactive oxygen (ROS) and nitrogen (NOS) or by secretion of cytokines including GM-CSF, IL-10, TGF-β that modulate T cell function. Tuberculosis and Human Immunodeficiency Virus infections constitute the main burden of infectious diseases worldwide, potentiate one another and accelerate disease development through various mechanisms which remain to be explored. Main objective: To determine and compare the mean frequencies of MDSCs, and function (in terms of levels of GM-CSF cytokine production) among HIV-positive patients co-infected with TB (TB/HIV) and HIV-positive patients without TB (HIV). Methodology : A PBMC assay and flow cytometry analysis was used to determine the frequencies of MDSCs of TB/HIV co-infected patients and HIV infected patients without TB as well as assess cytokine (GM-CSF) production by MDSCs upon stimulation with Pam3CSK4 and LPS. Fluorescently labelled antibodies against CD33, CD11b, CD66b, CD14, CD16, HLA-DR, and CD3 were used for cell surface staining and antibody labeled against GM-CSF for intracellular staining. Data was analyzed using Flowjo software and Mann-Whitney U test was used to compare frequencies between the groups. Statistical analysis was performed using GraphPad prism and p-values <0.05 were considered statistically significant. Results The frequency of total MDSCs, PM-MDSCs, and M-MDSCs in TB-HIV coinfected patients were slightly increased compared to HIV mono-infected patients, although the difference was not statistically significant (p=0.87949, p=0.3676, p=0.06931, respectively). Furthermore, there was significant (p=0.03345) decrease in production of GM-CSF in TB/HIV co-infected patients, compared to HIV-mono-infected patients. Conclusion The data reveal that MDSCs are induced in TB/HIV-1 coinfection and are associated with decreased GM-CSF production.