Contrasting Inflammatory Signatures in Peripheral Blood and Bronchoalveolar Cells Reveal Compartment-Specific Effects of HIV Infection
Year: 2020
Type: article
Study design: Observational Study
Abstract: The mechanisms by which HIV increases susceptibility to tuberculosis and other respiratory infections are incompletely understood. We used transcriptomics of paired whole bronchoalveolar lavage cells (BLCs) and peripheral blood mononuclear cells to compare the effect of HIV at the lung mucosal surface and in peripheral blood. The majority of HIV-induced differentially expressed genes (DEGs) were specific to either the peripheral or lung mucosa compartments (1,307/1,404, 93%). Type I interferon signaling was the dominant signature of DEGs in HIV-positive blood but not in HIV-positive BLCs. DEGs in the HIV-positive BLCs were significantly enriched for infiltration with cytotoxic CD8+ T cells. Higher expression of type 1 interferon transcripts in peripheral CD8+ T cells and representative transcripts and proteins in BLCs-derived CD8+ T cells during HIV infection, including IFNG (IFN-gamma), GZMB (Granzyme B) and PDCD1 (PD-1), was confirmed by cell-subset specific transcriptional analysis and flow cytometry. Thus, we report that a whole transcriptomic approach revealed qualitatively distinct effects of HIV in blood and bronchoalveolar compartments. Further work exploring the impact of distinct type I interferon programs and functional features of CD8+ T cells infiltrating the lung mucosa during HIV infection may provide novel insights into HIV-induced susceptibility to respiratory pathogens.
Source: Frontiers in Immunology
Authors: Daniel M. Muema, Maphe Mthembu, Abigail E. Schiff, Urisha Singh, Björn Corleis, Dongquan Chen, Thierry Bassett, Sipho S. Rasehlo, Kennedy Nyamande, Dilshaad Fakey Khan, Priya Maharaj, Mohammed Mitha, Moosa Suleman, Zoey Mhlane, Taryn Naidoo, Dirhona Ramjit, Farina Karim, Douglas S. Kwon, Thumbi Ndung'u, Emily B. Wong
Institutions: Kenya Medical Research Institute, Africa Health Research Institute, KEMRI-Wellcome Trust Research Programme, University of KwaZulu-Natal, Harvard University, Ragon Institute of MGH, MIT and Harvard, Friedrich-Loeffler-Institut, University of Alabama at Birmingham, Massachusetts General Hospital, Max Planck Institute for Infection Biology, University College London
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: Harvard University, Harvard University Center for AIDS Research, Wellcome Trust, Government of the United Kingdom, Department of Science and Innovation, South Africa, National Research Foundation, South African Medical Research Council, New Partnership for Africa's Development, African Academy of Sciences, Center for AIDS Research, University of Washington, Medical Research Council, Alliance for Accelerating Excellence in Science in Africa, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: G1203476693, G1575283533, G1722716446, G2415674080, G3000957577, G345173699, Medical Scientist Training Program, G4156438909, G4915094752, Sub-Saharan African Network for TB/HIV research Excellence (SANTHE), G5901762629, G6590892262, G6617178558, G6675272361, G6868616705, Studies of Mucosal Associated Invariant T (MAIT) cells in people with HIV, TB and HIV/TB co-infection in South Africa, G7785852513, G8183321107, G8445079486, G8488937646, G8547154903, Harvard University Center for AIDS Research, Sub-Saharan African Network for TB/HIV research Excellence (SANTHE)
OpenAlex ID: W3027382471