Identification of cytokine signatures in HIV-infected individuals with and without Mycobacterium tuberculosis co-infection

Abstract

Individuals with human immunodeficiency virus (HIV) infection are susceptible to immune system dysregulation, particularly during co-infection with Mycobacterium tuberculosis (MTB). Although there is an association between cytokine profiles and HIV-MTB co-infection, little is known about the cytokine-related host immune response mechanism to HIV-MTB co-infection. Therefore, the present study aimed to analyze expression of cytokines IL-17A, IFN-γ, TNF, IL-2, IL-10, IL-6 and IL-4 in individuals with HIV-MTB co-infection. A total of 30 patients with HIV and 40 with HIV-MTB co-infection were recruited into the present study, including those with active (A) (n=19) and latent (L)TB (n=21). HIV infection status was established based on national HIV guideline (Pedoman Nasional Pelayanan Kedokteran Tatalaksana HIV). ATB was confirmed using a positive acid-fast bacillus staining and culture of sputum; LTB status was established using IFN-γ release assay. Furthermore, the levels of cytokines IL-17A, IFN-γ, TNF, IL-10, IL-6, IL-4 and IL-2 were measured using flow cytometric bead array and CD4 cell count was performed by PIMA™ CD4 assay. IFN-γ, TNF, IL-10, IL-6 and IL-2 were able to significantly differentiate patients with HIV-ATB from those with HIV-LTB. Furthermore, in the patient subgroup with CD4 count <350 cells/µl, IFN-γ, IL-10 and IL-6 were able to differentiate between patients with HIV-ATB and HIV alone, as well as between patients with HIV-ATB and HIV-LTB. Based on these findings, the cytokine profiles are likely to be distinct between individuals with HIV infection with A- and LTB. Furthermore, the expression of CD4-positive T cells may influence the immune response in the body under HIV-MTB co-infection.