Work

CRTAM enhances T cell antimicrobial activity, particularly CD8+ T cells, against Mycobacterium tuberculosis infection

Year: 2026

Type: article

Abstract: Background The 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. Methods mRNA 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 . Results mRNA 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. Conclusions These 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.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1964260