ArticleThe Journal of infectious diseases2026
Restoration of Mucosa-Associated Invariant T-Cell Function in Healthcare-Associated Bacterial Infections Supports Recovery of Carbapenem Efficacy Against Resistant Bacteria Ex Vivo.
Article in The Journal of infectious diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAntimicrobial resistance (AMR) is a major challenge in healthcare-associated infections (HAIs), especially in immunocompromised individuals and those with comorbidities, who often have an impaired mucosa-associated invariant T (MAIT) cell pool. MAIT cells are innate-like T cells enriched in mucosal tissues with potent antimicrobial activity. Restoring their function may offer a host-directed strategy against drug-resistant pathogens.
methodsWe evaluated how cognate antigen in combination with cytokines modulates MAIT cell cytotoxicity and enhances carbapenem activity. MAIT cell cytolytic protein expression, cytotoxicity, and effector function were measured after stimulation. Secretomes from activated MAIT cells were tested against engineered Escherichia coli expressing clinically relevant carbapenemases.
resultsUnder optimal conditions, MAIT cells upregulated antimicrobial cytolytic proteins and efficiently killed antigen-pulsed target cells. Interleukin (IL)-15 or IL-2 plus IL-7 most effectively promoted polyfunctional cytotoxic responses. Secretomes from cytokine-stimulated MAIT cells restored imipenem activity against Escherichia coli expressing blaNDM-1, blaKPC-2, and blaOXA-48, reducing metabolic activity, viability, and growth. Notably, IL-2 plus IL-7 enabled expansion and functional restoration of MAIT cells from HAI patients with diminished baseline numbers and responses.
conclusionsTailored antigen and cytokine stimulation reinvigorates MAIT cell effector function and augments carbapenem efficacy, supporting MAIT cell-based host-directed adjunct strategies against AMR in vulnerable patients.
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