bims-maitce 2025-12-21 papers

Issue of 2025–12–21
two papers selected by
Andy E. Hogan, Maynooth University

J Exp Med. 2026 Mar 02. pii: e20241287. [Epub ahead of print]223(3):

Antibiotic use in early life impairs MAIT cell-mediated immunity in adulthood.

Gabrielle R LeBlanc, Adam L Sobel, Jonathan Melamed, Dominic Haas, Eduard Ansaldo, Aiko M Cirone, Elizabeth Murguia, Michael G Constantinides.

Mucosal-associated invariant T (MAIT) cells are predominantly located in barrier tissues where they rapidly respond to pathogens and commensals by recognizing microbial derivatives of riboflavin synthesis. Early-life exposure to these metabolites imprints the abundance of MAIT cells within tissues, so we hypothesized that antibiotic use during this period may abrogate their development. We identified antibiotics that deplete riboflavin-synthesizing commensals and revealed an early period of susceptibility during which antibiotic administration impaired MAIT cell development. The reduction in MAIT cell abundance rendered mice more susceptible to pneumonia, while MAIT cell-deficient mice were unaffected by early-life antibiotics. Concomitant administration of a riboflavin-synthesizing commensal during antibiotic treatment was sufficient to restore MAIT cell development and immunity. Our work demonstrates that transient depletion of riboflavin-synthesizing commensals in early life can adversely affect responses to subsequent infections.

DOI: https://doi.org/10.1084/jem.20241287

bioRxiv. 2025 Nov 25. pii: 2025.11.21.689870. [Epub ahead of print]

Restoration of MAIT cell function in healthcare-associated bacterial infections supports recovery of carbapenem efficacy against resistant bacteria.

Xue Yiting, Asad Mustafa Karim, Wan Rong Sia, Fei Han, Kai Lin Chan, Nathalie Grace Chua, Leila Hadadi, Zhenyu Liu, Jeffrey Yw Mak, David P Fairlie, Lin-Fa Wang, Johan K Sandberg, Andrea Lay-Hoon Kwa, Edwin Leeansyah.

Antimicrobial resistance (AMR) presents a major clinical challenge to patients with healthcare-associated infections (HAIs), particularly among immunocompromised individuals and patients with comoribidites, who often exhibit an impaired mucosa-associated invariant T (MAIT) cell pool. MAIT cells are innate-like T cells enriched in mucosal tissues, possess potent antibacterial activity, and restoration of their function may offer a host-directed strategy against drug-resistant pathogens. We evaluated how stimulation with cognate antigen in combination with various cytokines, modulates MAIT cell cytotoxicity and enhances carbapenem activity. Under optimal conditions, MAIT cells exhibited increased expression of antimicrobial cytolytic proteins and efficiently killed cells pulsed with MAIT cell antigen. IL-15 or IL-2 plus IL-7 were particularly effective in promoting polyfunctional cytotoxic responses. Secretomes from cytokine-stimulated MAIT cells restored the activity of imipenem against engineered E. coli expressing the clinically relevant carbapenemases bla NDM-1 , bla KPC-2 , and bla OXA-48 , strongly reducing bacterial growth, viability, and metabolic activity. Notably, IL-2 plus IL-7 stimulation enabled expansion and functional restoration of MAIT cells from HAI patients, whose baseline MAIT cell numbers and responses were diminished. These findings demonstrate that tailored stimulation can reinvigorate MAIT cell effector function and augment antibiotic efficacy, supporting a role for MAIT cells in adjunct immunotherapeutic strategy to combat AMR in vulnerable patient populations. Category of manuscript: Research Article.

DOI: https://doi.org/10.1101/2025.11.21.689870