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Tetraspanin CD82 restrains phagocyte migration but supports macrophage activation

ABSTRACT: Summary Phagocytes migrate into tissues to combat infection and maintain tissue homeostasis. As dysregulated phagocyte migration and function can lead to inflammation or susceptibility to infection, identifying molecules that control these processes is critical. Here, we show that the tetraspanin CD82 restrains the migration of neutrophils and macrophages into tissues. Cd82−/− phagocytes exhibited excessive migration during in vivo models of peritoneal inflammation, superfusion of CXCL1, retinopathy of prematurity, and infection with the protozoan parasite L. mexicana. However, with the latter, while Cd82−/− macrophages infiltrated infection sites at higher proportions, cutaneous L. mexicana lesions were larger and persisted, indicating a failure to control infection. Analyses of in vitro bone-marrow-derived macrophages showed CD82 deficiency altered cellular morphology, and impaired gene expression and metabolism in response to anti-inflammatory activation. Altogether, this work reveals an important role for CD82 in restraining phagocyte infiltration and mediating their differentiation in response to stimulatory cues. Graphical abstract Highlights • Tetraspanin CD82 restrains phagocyte migration in murine models of inflammation• Excessive migration of Cd82−/− myeloid cells exacerbates retinal inflammation• Cd82−/− macrophages have a reduced ability to clear Leishmania mexicana parasites• CD82 is required for the normal morphology and activation of M2 macrophages Biological sciences; Immunology; Immune system

SUBMITTER: McGowan E

PROVIDER: S-EPMC9213772 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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