CD4 T cells are rapidly depleted from tuberculosis granulomas following acute SIV co-infection

Taylor W Foreman; Christine E Nelson; Keith D Kauffman; Nickiana E Lora; Caian L Vinhaes; Danielle E Dorosky; Shunsuke Sakai; Felipe Gomez; Joel D Fleegle; Melanie Parham; Shehan R Perera; Cecilia S Lindestam Arlehamn; Alessandro Sette; Tuberculosis Imaging Program; Jason M Brenchley; Artur T L Queiroz; Bruno B Andrade; Juraj Kabat; Laura E Via; Daniel L Barber

doi:10.1016/j.celrep.2022.110896

CD4 T cells are rapidly depleted from tuberculosis granulomas following acute SIV co-infection

Cell Rep. 2022 May 31;39(9):110896. doi: 10.1016/j.celrep.2022.110896.

Authors

Taylor W Foreman¹, Christine E Nelson¹, Keith D Kauffman¹, Nickiana E Lora¹, Caian L Vinhaes², Danielle E Dorosky¹, Shunsuke Sakai¹, Felipe Gomez³, Joel D Fleegle³, Melanie Parham⁴, Shehan R Perera⁵, Cecilia S Lindestam Arlehamn⁶, Alessandro Sette⁶; Tuberculosis Imaging Program³; Jason M Brenchley⁷, Artur T L Queiroz⁸, Bruno B Andrade², Juraj Kabat⁹, Laura E Via¹⁰, Daniel L Barber¹¹

Affiliations

¹ T lymphocyte Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA.
² Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA 41810-710, Brazil; Bahiana School of Medicine and Public Health (EBMSP), Salvador, BA 40296, Brazil.
³ Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA.
⁴ Axle Informatics, National Center for Advancing Translational Sciences, Bethesda, MD 20892, USA.
⁵ Department of Electrical and Computer Engineering, The Ohio State University, Columbus, OH 43201, USA.
⁶ Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
⁷ Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA.
⁸ Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA 41810-710, Brazil; Data and Knowledge Integration Center for Health (CIDACS), Instituto Gonçalo Moniz, Salvador, BA 40296, Brazil.
⁹ Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA.
¹⁰ Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA; Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA; Institute of Infectious Disease & Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Observatory, Cape Town, 7925, South Africa.
¹¹ T lymphocyte Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: barberd@niaid.nih.gov.

PMID: 35649361
DOI: 10.1016/j.celrep.2022.110896

Abstract

HIV/Mycobacterium tuberculosis (Mtb) co-infected individuals have an increased risk of tuberculosis prior to loss of peripheral CD4 T cells, raising the possibility that HIV co-infection leads to CD4 T cell depletion in lung tissue before it is evident in blood. Here, we use rhesus macaques to study the early effects of simian immunodeficiency virus (SIV) co-infection on pulmonary granulomas. Two weeks after SIV inoculation of Mtb-infected macaques, Mtb-specific CD4 T cells are dramatically depleted from granulomas, before CD4 T cell loss in blood, airways, and lymph nodes, or increases in bacterial loads or radiographic evidence of disease. Spatially, CD4 T cells are preferentially depleted from the granuloma core and cuff relative to B cell-rich regions. Moreover, live imaging of granuloma explants show that intralesional CD4 T cell motility is reduced after SIV co-infection. Thus, granuloma CD4 T cells may be decimated before many co-infected individuals experience the first symptoms of acute HIV infection.

Keywords: CD4 T cells; CP: Immunology; CP: Microbiology; SIV; granulomas; live imaging; tuberculosis.

Published by Elsevier Inc.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural

MeSH terms

Animals
CD4-Positive T-Lymphocytes
Coinfection* / pathology
Granuloma / pathology
HIV Infections* / complications
HIV Infections* / pathology
Macaca mulatta
Simian Acquired Immunodeficiency Syndrome* / complications
Simian Acquired Immunodeficiency Syndrome* / pathology
Simian Immunodeficiency Virus*
Tuberculosis* / pathology