CD209d/e are required for macrophage-mediated phagocytosis and activation during methicillin-resistant Staphylococcus...

Staphylococcus aureus is a commensal and opportunist pathogen of the upper respiratory tract. The recognition of pathogen-associated molecular patterns through pattern-recognition receptors is crucial for eliminating microorganisms such as S. aureus. DC-SIGN (CD209) is a pattern-recognition receptor that binds to a broad range of pathogens, promoting phagocytosis. Here we aimed to study the role of mouse homologues of DC-SIGN, CD209d/e, in a methicillin-resistant S. aureus (MRSA) pulmonary infection model. CD209d/e-/- and wild-type C57BL/6 mice were infected with MRSA and inflammatory parameters were evaluated. CD209d/e-/- mice had delayed bacterial burden and mortality together with increased frequency of neutrophils and decreased dendritic cells in the lung compared with control mice. iNOS+ macrophages, and regulatory T cell frequency were decreased in the lungs of CD209d/e-/- mice. CD209d/e-/- mice had increased levels of inflammatory cytokines in the lungs, but levels of IL-12p40 were decreased. MRSA reduced expression of interferon-γ and pattern-recognition receptors in CD209d/e-/- mice. MRSA uptake by phagocytes was decreased in the lungs of CD209d/e-/- versus control mice. CD209d/e-/- bone marrow derived macrophages showed impaired MRSA uptake and killing. These data suggest that CD209d/e are essential receptors to control inflammation by activating macrophages leading to MRSA uptake and killing.