Dysfunctional bronchoalveolar effector memory CD8+ T cells in tuberculosis-exposed people living with antiretroviral-naïve HIV infection
HIV causes susceptibility to respiratory pathogens, including tuberculosis (TB), but the underlying immunological mechanisms remain incompletely understood. We obtained whole blood and bronchoalveolar lavage (BAL) from TB-exposed people in the presence or absence of antiretroviral-naïve HIV co-infection. Bulk transcriptional profiling demonstrated compartment-specific enrichment of immunological processes. Systems-level deconvolution of whole blood from people living with HIV identified elevated type I and type II interferon cytokine activity and T cell proliferation. Transcriptional modules derived from both peripheral blood and sorted BAL immune cells demonstrated an increased frequency of effector memory CD8 T cells in whole BAL samples. Both compartments displayed reduced induction of CD8 T-cell-derived interleukin-17A (IL-17A) in people with HIV, associated with elevated T cell regulatory molecule expression. The data suggest that dysfunctional CD8 T cell responses in uncontrolled HIV may contribute to compromised respiratory immunity to pathogens, a process that could be modulated by host-directed therapies that target CD8 T cell effector functions.
Authors
- Mohammed Mitha (ORCID: https://orcid.org/0000-0003-1916-8201)
- Zoey Mhlane
- Jan Wilhelm Spillner (ORCID: https://orcid.org/0000-0002-9759-1892)
- Valentin Voillet (ORCID: https://orcid.org/0000-0002-5751-3881)
- Dilshaad Fakey Khan (ORCID: https://orcid.org/0000-0003-0665-792X)
- Priya Maharaj
- Thumbi Ndung’u (ORCID: https://orcid.org/0000-0003-2962-3992)
- Emily Wong
- Kennedy Nyamande (ORCID: https://orcid.org/0000-0002-8515-0774)
- Gabriele Pollara (ORCID: https://orcid.org/0000-0001-5772-0322)
- Farina Karim (ORCID: https://orcid.org/0000-0001-9698-016X)
- Maphe Mthembu (ORCID: https://orcid.org/0000-0003-1077-6403)
- Erica Andersen‐Nissen (ORCID: https://orcid.org/0000-0001-9213-920X)
- Sharon Khuzwayo (ORCID: https://orcid.org/0000-0003-4482-5955)
- Anneta Naidoo
- Helgard Claassen
Institutions
- Ragon Institute of MGH, MIT and Harvard (US)
- University of Alabama at Birmingham (US)
- Africa Health Research Institute (ZA)
- The London College (GB)
- University of KwaZulu-Natal (ZA)
Publication Details
- Journal
- iScience
- Published
- 2024-10-16
- DOI
- https://doi.org/10.1016/j.isci.2024.111137
- Primary Topic
- Pneumocystis jirovecii pneumonia detection and treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Burroughs Wellcome Fund
- American Society of Tropical Medicine and Hygiene
- Wellcome Trust
- Government of the United Kingdom
- Department of Science and Innovation, South Africa
- University College London
- South African Medical Research Council
- New Partnership for Africa's Development
- Animal Health Research Institute
- Victor Daitz Foundation
- National Institutes of Health
- UCLH Biomedical Research Centre
- National Institute on Aging
- National Institute of Allergy and Infectious Diseases