Contrasting inflammatory signatures in peripheral blood and bronchoalveolar cells reveal compartment-specific effects of HIV infection
Year: 2019
Type: preprint
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 (BAL) fluid and peripheral blood mononuclear cells to compare the effect of HIV at the lung mucosal surface and in the peripheral blood. The large 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 with a less dominant and qualitatively distinct type I interferon gene set expression pattern in HIV-positive BAL. DEGs in the HIV-positive BAL were significantly enriched for infiltration with cytotoxic CD8 + T cells. Higher expression of representative transcripts and proteins in BAL CD8 + T cells during HIV infection, including IFNG (IFN-γ), 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 CD8 + T cells infiltration of the lung mucosa during HIV infection may provide novel insights into HIV-induced susceptibility to respiratory pathogens.
DOI: 10.1101/804229
Authors: Daniel M. Muema, Maphe Mthembu, Abigail Schiff, Urisha Singh, Bj□rn Corleis, 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, Massachusetts Institute of Technology, Friedrich-Loeffler-Institut, Max Planck Institute for Infection Biology, University College London, Massachusetts General Hospital
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: Harvard University, Harvard University Center for AIDS Research, Wellcome Trust, National Research Foundation, South African Medical Research Council, Victor Daitz Foundation, National Institutes of Health, Center for AIDS Research, University of Washington, Medical Research Council, National Institute of Allergy and Infectious Diseases
OpenAlex ID: W2981776986