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CD4 + TÂ cells re-wire granuloma cellularity and regulatory networks to promote immunomodulation following Mtb reinfection.
- Source :
-
Immunity [Immunity] 2024 Oct 08; Vol. 57 (10), pp. 2380-2398.e6. Date of Electronic Publication: 2024 Aug 29. - Publication Year :
- 2024
-
Abstract
- Immunological priming-in the context of either prior infection or vaccination-elicits protective responses against subsequent Mycobacterium tuberculosis (Mtb) infection. However, the changes that occur in the lung cellular milieu post-primary Mtb infection and their contributions to protection upon reinfection remain poorly understood. Using clinical and microbiological endpoints in a non-human primate reinfection model, we demonstrated that prior Mtb infection elicited a long-lasting protective response against subsequent Mtb exposure and was CD4 <superscript>+</superscript> T cell dependent. By analyzing data from primary infection, reinfection, and reinfection-CD4 <superscript>+</superscript> T cell-depleted granulomas, we found that the presence of CD4 <superscript>+</superscript> T cells during reinfection resulted in a less inflammatory lung milieu characterized by reprogrammed CD8 <superscript>+</superscript> T cells, reduced neutrophilia, and blunted type 1 immune signaling among myeloid cells. These results open avenues for developing vaccines and therapeutics that not only target lymphocytes but also modulate innate immune cells to limit tuberculosis (TB) disease.<br />Competing Interests: Declaration of interests A.K.S. reports compensation for consulting and/or scientific advisory board membership from Honeycomb Biotechnologies, Cellarity, Ochre Bio, Relation Therapeutics, Fog Pharma, Passkey Therapeutics, IntrECate Biotherapeutics, Bio-Rad Laboratories, and Dahlia Biosciences unrelated to this work. S.M.F. reports compensation for board of directors’ membership from Oxford Nanopore unrelated to this work. J.L.F. reports compensation for consulting for Janssen Inc. and scientific advisory board membership for the Nonhuman Primate Research Resource unrelated to this work. After submission of this publication, J.M.R. began employment with Merck & Co., Cambridge, MA, USA. He did not conduct work on this publication after his employment at Merck & Co.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Tuberculosis immunology
Tuberculosis microbiology
Disease Models, Animal
Lung immunology
Lung microbiology
Lung pathology
Humans
Tuberculosis, Pulmonary immunology
Tuberculosis, Pulmonary microbiology
CD4-Positive T-Lymphocytes immunology
Mycobacterium tuberculosis immunology
Reinfection immunology
Immunomodulation
Granuloma immunology
Granuloma microbiology
CD8-Positive T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4180
- Volume :
- 57
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 39214090
- Full Text :
- https://doi.org/10.1016/j.immuni.2024.08.002