CRTAM enhances T cell antimicrobial activity, particularly CD8+ T cells, against Mycobacterium tuberculosis infection
4 affiliations
- 1Shanghai Clinical Research Center for Infectious Disease (tuberculosis), Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Institute for Advanced Study, Tongji University School of Medicine, Shanghai, China
- 2Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
- 3Department of Clinical Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
- 4Shanghai Sci-Tech Inno Center for Infection and Immunity, Shanghai, China
Abstract
BackgroundThe mechanisms underpinning protective host immunity against Mycobacterium tuberculosis (Mtb) are not fully elucidated. Resisters, individuals with prolonged exposure to Mtb who remain negative on repeated immunological testing for Mtb infection, provide a unique opportunity to investigate protective immune responses. This study systematically investigated the functional characteristics of CXCR3+CD107a+ effector cells in Resisters to identify molecules potentially associated with protective anti-mycobacterial immunity.MethodsmRNA sequencing was employed to investigate the transcriptional characteristics of CXCR3+CD107a+ effector lymphocytes from Resisters and tuberculosis patients. Flow cytometry was utilized to assess CRTAM expression and effector phenotypes, and colony-forming units assays quantified the bacterial burdens in infected macrophages. Crtam-deficient and wild-type mice were used to investigate the function of CRTAM to host control of mycobacterial infection in vivo.ResultsmRNA sequencing of CXCR3+CD107a+ effector lymphocytes isolated from Resisters revealed elevated CRTAM expression, which positively correlated with anti-mycobacterial effector molecules. CRTAM levels were lower in patients with chronic Mtb infection. Mycobacterial stimulation rapidly increased CRTAM expression, particularly in CD8+ T cells. CRTAM expression and agonistic CRTAM stimulation were associated with enhanced T-cell effector responses and inhibition of intracellular mycobacterial growth. Crtam-deficient mice showed increased susceptibility to mycobacterial infection, whereas recombinant CRTAM administration conferred significant immune protection.ConclusionsThese findings identify CRTAM as a protective immune-associated molecule that contributes to anti-mycobacterial effector responses. The recombinant CRTAM findings provided initial in vivo proof-of-concept that CRTAM can modulate infection-associated outcomes during Mtb infection, supporting its further investigation as an immune-regulatory molecule.
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BibTeX
@article{peng2026crtam,
title = {{CRTAM enhances T cell antimicrobial activity, particularly CD8+ T cells, against Mycobacterium tuberculosis infection}},
author = {Ying Peng and Juechu Wang and Xuejiao Ji and Guixian Huang and Liying Zhu and Yuan Wu and Xiaocui Wu and Wei Sha and Feifei Wang and Hongbo Shen and Hongbo Shen},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1964260},
url = {https://doi.org/10.3389/fimmu.2026.1964260},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - CRTAM enhances T cell antimicrobial activity, particularly CD8+ T cells, against Mycobacterium tuberculosis infection
AU - Ying Peng
AU - Juechu Wang
AU - Xuejiao Ji
AU - Guixian Huang
AU - Liying Zhu
AU - Yuan Wu
AU - Xiaocui Wu
AU - Wei Sha
AU - Feifei Wang
AU - Hongbo Shen
AU - Hongbo Shen
PY - 2026
DA - 2026/10/23
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1964260
UR - https://doi.org/10.3389/fimmu.2026.1964260
AB - BackgroundThe mechanisms underpinning protective host immunity against Mycobacterium tuberculosis (Mtb) are not fully elucidated. Resisters, individuals with prolonged exposure to Mtb who remain negative on repeated immunological testing for Mtb infection, provide a unique opportunity to investigate protective immune responses. This study systematically investigated the functional characteristics of CXCR3+CD107a+ effector cells in Resisters to identify molecules potentially associated with protective anti-mycobacterial immunity.MethodsmRNA sequencing was employed to investigate the transcriptional characteristics of CXCR3+CD107a+ effector lymphocytes from Resisters and tuberculosis patients. Flow cytometry was utilized to assess CRTAM expression and effector phenotypes, and colony-forming units assays quantified the bacterial burdens in infected macrophages. Crtam-deficient and wild-type mice were used to investigate the function of CRTAM to host control of mycobacterial infection in vivo.ResultsmRNA sequencing of CXCR3+CD107a+ effector lymphocytes isolated from Resisters revealed elevated CRTAM expression, which positively correlated with anti-mycobacterial effector molecules. CRTAM levels were lower in patients with chronic Mtb infection. Mycobacterial stimulation rapidly increased CRTAM expression, particularly in CD8+ T cells. CRTAM expression and agonistic CRTAM stimulation were associated with enhanced T-cell effector responses and inhibition of intracellular mycobacterial growth. Crtam-deficient mice showed increased susceptibility to mycobacterial infection, whereas recombinant CRTAM administration conferred significant immune protection.ConclusionsThese findings identify CRTAM as a protective immune-associated molecule that contributes to anti-mycobacterial effector responses. The recombinant CRTAM findings provided initial in vivo proof-of-concept that CRTAM can modulate infection-associated outcomes during Mtb infection, supporting its further investigation as an immune-regulatory molecule.
SN - 1664-3224
ER -