CD4+T cells from HIV-1 patients with impaired Th1 effector responses to Mycobacterium tuberculosis exhibit diminished histone and nucleoprotein signatures

摘要

HIV + patients have an increased risk for tuberculosis disease despite clinical management with ARTs. We established a culture model of Mtb-infection in PBMCs from HIV + PPD + donors on suppressive ART (median 6.4 years) with negligible viral loads (median < 50 copies/mL) and stable CD4+T cell counts (517 cells/mm<^>3). We observed that HIV+patient lymphocytes harbored a recruitment defect to Mtb-infected monocytes. To investigate these immune defects on a per cell basis, purified CD4 + T cells from HIV patients were assessed by label-free quantification protein mass spectrometry. CD4 + T cells from HIV patients displayed diminished nucleoprotein levels - notably of histone variant H2a.Z and ribonucleoprotein Al. Only within healthy donors, transcriptional regulatory histone variant H2a.Z expression was correlated to the extent of IFN-gamma induction upon Mtb-infection. Our findings may explain why HIV patients exhibit prolonged immune cell dysfunction despite suppressive ART, and implicate a per cell defect of CD4+ T cells. (C) 2017 Published by Elsevier Inc.