Influenza-induced immune suppression to methicillin-resistant Staphylococcus aureus is mediated by TLR9

摘要: Bacterial lung infections, particularly with methicillin-resistant Staphylococcus aureus (MRSA), increase mortality following influenza infection, but the mechanisms remain unclear. Here we show that expression of TLR9, a microbial DNA sensor, is increased in murine macrophages, dendritic cells, CD8+ T cells and epithelial post-influenza infection. TLR9-/- mice did not differences handling nor MRSA infection alone. However, have improved survival bacterial clearance dual no difference viral load during We demonstrate TLR9 upregulated on macrophages even when they are themselves infected, suggesting upregulation related to soluble mediators. rule out role for elevations interferon-γ (IFNγ) mediating beneficial mice. While from WT similar phagocytosis killing alone, there marked scavenger receptor A as well inducible nitric oxide synthase (Inos) specific TLR9-deficient cells. Bone marrow transplant chimera experiments vitro using antagonists suggest non-hematopoietic rather than themselves, important regulating myeloid cell function. Interestingly, post-dual was restricted MRSA, Streptococcus pneumoniae. Taken together these data surprising inhibitory signaling manifests