Dysfunctional bronchoalveolar effector memory CD8+ T cells in tuberculosis-exposed people living with antiretroviral-naïve HIV infection
Maphe Mthembu,
Helgard Claassen,
Sharon Khuzwayo,
Valentin Voillet,
Anneta Naidoo,
Jule S. Spillner,
Kennedy Nyamande,
Dilshaad Fakey Khan,
Priya Maharaj,
Mohammed Mitha,
Zoey Mhlane,
Farina Karim,
Erica Andersen-Nissen,
Thumbi Ndung’u,
Gabriele Pollara,
Emily B. Wong
Affiliations
Maphe Mthembu
Africa Health Research Institute, Durban, South Africa; University of KwaZulu-Natal, Medical School, Durban, South Africa
Helgard Claassen
Africa Health Research Institute, Durban, South Africa; University of KwaZulu-Natal, Medical School, Durban, South Africa
Sharon Khuzwayo
Africa Health Research Institute, Durban, South Africa; University of KwaZulu-Natal, Medical School, Durban, South Africa; Cape Town HVTN Immunology Laboratory, Cape Town, South Africa
Valentin Voillet
Cape Town HVTN Immunology Laboratory, Cape Town, South Africa
Anneta Naidoo
Cape Town HVTN Immunology Laboratory, Cape Town, South Africa
Jule S. Spillner
Division of Infection and Immunity, University London College, London, UK
Kennedy Nyamande
Department of Pulmonology, Inkosi Albert Luthuli Central Hospital, Durban, South Africa
Dilshaad Fakey Khan
Department of Pulmonology, Inkosi Albert Luthuli Central Hospital, Durban, South Africa
Priya Maharaj
Department of Pulmonology, Inkosi Albert Luthuli Central Hospital, Durban, South Africa
Mohammed Mitha
Department of Pulmonology, Inkosi Albert Luthuli Central Hospital, Durban, South Africa
Zoey Mhlane
Africa Health Research Institute, Durban, South Africa
Farina Karim
Africa Health Research Institute, Durban, South Africa; University of KwaZulu-Natal, Medical School, Durban, South Africa
Erica Andersen-Nissen
Cape Town HVTN Immunology Laboratory, Cape Town, South Africa
Thumbi Ndung’u
Africa Health Research Institute, Durban, South Africa; University of KwaZulu-Natal, Medical School, Durban, South Africa; Department of Pulmonology, Inkosi Albert Luthuli Central Hospital, Durban, South Africa; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA
Gabriele Pollara
Division of Infection and Immunity, University London College, London, UK; Corresponding author
Emily B. Wong
Africa Health Research Institute, Durban, South Africa; Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA; Corresponding author
Summary: 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.
