The CD36 and SR-A/CD204 scavenger receptors fine-tune Staphylococcus aureus-stimulated cytokine production in mouse macrophages

• Published in: Cellular immunology 2022-02, Vol.372, p.104483-104483, Article 104483
• Main Authors: Peruń, Angelika, Gębicka, Magdalena, Biedroń, Rafał, Skalska, Paulina, Józefowski, Szczepan
• Format: Article
• Language: English
• Subjects: Animals; CD14; CD204; CD36; CD36 Antigens - deficiency; CD36 Antigens - genetics; CD36 Antigens - immunology; Cytokine; Cytokines - biosynthesis; Endocytosis; Endocytosis - immunology; Ligands; Lipopolysaccharide Receptors - immunology; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - microbiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Phagocytosis; Receptors, Pattern Recognition - immunology; Scavenger receptors; Scavenger Receptors, Class A - deficiency; Scavenger Receptors, Class A - genetics; Scavenger Receptors, Class A - immunology; Signal Transduction - immunology; Staphylococcus aureus; Staphylococcus aureus - immunology; Staphylococcus aureus - pathogenicity; Toll-like receptor 2; Toll-Like Receptor 2 - immunology
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2022.104483

•TLR2 mediates S. aureus-stimulated cytokine production in macrophages.•Dynamin-dependent endocytosis preconditions intracellular activation of TLR2.•CD36 and SR-A/CD204 link CD14 and TLR2 endocytosis to a dynamin-dependent pathway.•TLR2 induces TNF-α production in early and then IL-6 production in late endosomes.•Autonomous SR-A and CD36 signaling inhibits cytokine production. The occurring in SR-A/CD204- or CD36-deficient mice increased susceptibility to infections with Staphylococcus aureus (Sa) had traditionally been ascribed to the impairment of macrophage-mediated phagocytosis, which is, however, inconsistent with low effectiveness of unopsonized Sa killing within macrophages and redundant roles of both receptors in this process. We have found that Sa-stimulated cytokine production in mouse macrophages seems to be exclusively mediated by TLR2, mainly from within endosomes in response to Sa-derived lipoteichoic acid. By driving endocytic trafficking of TLR2 and its ligands through the clathrin-dependent pathway, CD36 and SR-A sensitize macrophages to activation by Sa as well as regulate the type and amount of cytokines produced. Additionally, upon direct Sa binding, both receptors autonomously generate anti-inflammatory signaling. Consequently, the delayed induction of acute inflammation in knockout mice may allow for the initial, uncontrolled multiplication of bacteria, stimulating excessive, septic shock-inducing production of inflammatory cytokines in later stages of infection.