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Pulmonary Mycobacterium tuberculosis control associates with CXCR3- and CCR6-expressing antigen-specific Th1 and Th17 cell recruitment
Uma Shanmugasundaram, … , Deepak Kaushal, Jyothi Rengarajan
Uma Shanmugasundaram, … , Deepak Kaushal, Jyothi Rengarajan
Published June 17, 2020
Citation Information: JCI Insight. 2020;5(14):e137858. https://doi.org/10.1172/jci.insight.137858.
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Research Article Immunology Infectious disease

Pulmonary Mycobacterium tuberculosis control associates with CXCR3- and CCR6-expressing antigen-specific Th1 and Th17 cell recruitment

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Abstract

Mycobacterium tuberculosis–specific (M. tuberculosis–specific) T cell responses associated with immune control during asymptomatic latent tuberculosis infection (LTBI) remain poorly understood. Using a nonhuman primate aerosol model, we studied the kinetics, phenotypes, and functions of M. tuberculosis antigen-specific T cells in peripheral and lung compartments of M. tuberculosis–infected asymptomatic rhesus macaques by longitudinally sampling blood and bronchoalveolar lavage, for up to 24 weeks postinfection. We found substantially higher frequencies of M. tuberculosis–specific effector and memory CD4+ and CD8+ T cells producing IFN-γ in the airways compared with peripheral blood, and these frequencies were maintained throughout the study period. Moreover, M. tuberculosis–specific IL-17+ and IL-17+IFN-γ+ double-positive T cells were present in the airways but were largely absent in the periphery, suggesting that balanced mucosal Th1/Th17 responses are associated with LTBI. The majority of M. tuberculosis–specific CD4+ T cells that homed to the airways expressed the chemokine receptor CXCR3 and coexpressed CCR6. Notably, CXCR3+CD4+ cells were found in granulomatous and nongranulomatous regions of the lung and inversely correlated with M. tuberculosis burden. Our findings provide insights into antigen-specific T cell responses associated with asymptomatic M. tuberculosis infection that are relevant for developing better strategies to control TB.

Authors

Uma Shanmugasundaram, Allison N. Bucsan, Shashank R. Ganatra, Chris Ibegbu, Melanie Quezada, Robert V. Blair, Xavier Alvarez, Vijayakumar Velu, Deepak Kaushal, Jyothi Rengarajan

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Figure 1

Experimental design and clinical characteristics of asymptomatic rhesus macaques with LTBI.

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Experimental design and clinical characteristics of asymptomatic rhesus ...
(A) Eight rhesus macaques were infected by low-dose aerosol route with M. tuberculosis CDC1551 at week 0, and infection was confirmed at 3 and 7 weeks by TST and IGRA tests. Six macaques were defined as LTBI based on absence of clinical signs and symptoms of disease and a negative chest x-ray up to week 15. Six animals remained asymptomatic and were longitudinally followed up until week 24. PBMCs and BAL were collected at indicated time points, and lung tissues were collected at necropsy. Each colored symbol represents an animal. (B) CRP levels were measured before infection (week –1) and at indicated time points postinfection for n = 6 animals. (C) M. tuberculosis burden (CFU) in BAL measured at indicated weeks. (D) M. tuberculosis burden (CFU) in lung at necropsy (CFU per gram of tissue plated). (E) Percentage of granuloma in the lung tissue, determined by dividing the granulomatous area (mm2) by the area of the annotated regions (mm2) classified using an algorithm trained via a deep convolutional network (HALO AI).

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

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