Frontiers in Immunology (May 2020)
Contrasting Inflammatory Signatures in Peripheral Blood and Bronchoalveolar Cells Reveal Compartment-Specific Effects of HIV Infection
- Daniel M. Muema,
- Daniel M. Muema,
- Daniel M. Muema,
- Maphe Mthembu,
- Abigail E. Schiff,
- Abigail E. Schiff,
- Urisha Singh,
- Björn Corleis,
- 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,
- Douglas S. Kwon,
- Douglas S. Kwon,
- Thumbi Ndung'u,
- Thumbi Ndung'u,
- Thumbi Ndung'u,
- Thumbi Ndung'u,
- Thumbi Ndung'u,
- Emily B. Wong,
- Emily B. Wong,
- Emily B. Wong,
- Emily B. Wong
Affiliations
- Daniel M. Muema
- African Health Research Institute, Durban, South Africa
- Daniel M. Muema
- HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa
- Daniel M. Muema
- KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
- Maphe Mthembu
- African Health Research Institute, Durban, South Africa
- Abigail E. Schiff
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, United States
- Abigail E. Schiff
- Department of Medicine, Harvard Medical School, Boston, MA, United States
- Urisha Singh
- African Health Research Institute, Durban, South Africa
- Björn Corleis
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, United States
- Björn Corleis
- Institute of Immunology, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Greifswald, Isle of Riems, Germany
- Dongquan Chen
- Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL, United States
- Thierry Bassett
- African Health Research Institute, Durban, South Africa
- Sipho S. Rasehlo
- African Health Research Institute, Durban, South Africa
- Kennedy Nyamande
- Department of Pulmonology, Inkosi Albert Luthuli Central Hospital, Nelson R. Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
- Dilshaad Fakey Khan
- Department of Pulmonology, Inkosi Albert Luthuli Central Hospital, Nelson R. Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
- Priya Maharaj
- Department of Pulmonology, Inkosi Albert Luthuli Central Hospital, Nelson R. Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
- Mohammed Mitha
- Department of Pulmonology, Inkosi Albert Luthuli Central Hospital, Nelson R. Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
- Moosa Suleman
- Department of Pulmonology, Inkosi Albert Luthuli Central Hospital, Nelson R. Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
- Zoey Mhlane
- African Health Research Institute, Durban, South Africa
- Taryn Naidoo
- African Health Research Institute, Durban, South Africa
- Dirhona Ramjit
- African Health Research Institute, Durban, South Africa
- Farina Karim
- African Health Research Institute, Durban, South Africa
- Douglas S. Kwon
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, United States
- Douglas S. Kwon
- Department of Medicine, Harvard Medical School, Boston, MA, United States
- Douglas S. Kwon
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, United States
- Thumbi Ndung'u
- African Health Research Institute, Durban, South Africa
- Thumbi Ndung'u
- HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa
- Thumbi Ndung'u
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, United States
- Thumbi Ndung'u
- 0Division of Infection and Immunity, University College London, London, United Kingdom
- Thumbi Ndung'u
- 1Max Planck Institute for Infection Biology, Berlin, Germany
- Emily B. Wong
- African Health Research Institute, Durban, South Africa
- Emily B. Wong
- Department of Medicine, Harvard Medical School, Boston, MA, United States
- Emily B. Wong
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, United States
- Emily B. Wong
- 0Division of Infection and Immunity, University College London, London, United Kingdom
- DOI
- https://doi.org/10.3389/fimmu.2020.00864
- Journal volume & issue
-
Vol. 11
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.
Keywords
