Deficiency in non-classical major histocompatibility class II-like molecule, H2-O confers protection against Staphylococcus aureus in mice.

Staphylococcus aureus is a human-adapted pathogen that replicates by asymptomatically colonizing its host. S. aureus is also the causative agent of purulent skin and soft tissue infections as well as bloodstream infections that result in the metastatic seeding of abscess lesions in all organ tissues. Prolonged colonization, infection, disease relapse, and recurrence point to the versatile capacity of S. aureus to bypass innate and adaptive immune defenses as well as the notion that some hosts fail to generate protective immune responses. Here, we find a genetic trait that provides protection against this pathogen. Mice lacking functional H2-O, the equivalent of human HLA-DO, inoculated with a mouse-adapted strain of S. aureus, efficiently decolonize the pathogen. Further, these decolonized animals resist subsequent bloodstream challenge with methicillin-resistant S. aureus. A genetic approach demonstrates that T-cell dependent B cell responses are required to control S. aureus colonization and infection in H2-O-deficient mice. Reduced bacterial burdens in these animals correlate with increased titers and enhanced phagocytic activity of S. aureus-specific antibodies. H2-O negatively regulates the loading of high affinity peptides on major histocompatibility class II (MHC-II) molecules. Thus, we hypothesize that immune responses against S. aureus are derepressed in mice lacking H2-O because more high affinity peptides are presented by MHC-II. We speculate that loss-of-function HLA-DO alleles may similarly control S. aureus replication in humans.

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Copyright: © 2024 Cullum et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.