Streptococci are common human colonizers with a species-specific mucocutaneous distribution. At the same time, they are among the most important and most virulent invasive bacterial pathogens. Thus, site-specific cellular innate immunity, which is predominantly executed by resident and invading myeloid cells, has to be adapted with respect to streptococcal sensing, handling, and response. In this article, we show that TLR13 is the critical mouse macrophage (MPhi) receptor in the response to group B Streptococcus, both in bone marrow-derived MPhis and in mature tissue MPhis, such as those residing in the lamina propria of the colon and the dermis, as well as in microglia. In contrast, TLR13 and its chaperone UNC-93B are dispensable for a potent cytokine response of blood monocytes to group B Streptococcus, although monocytes serve as the key progenitors of intestinal and dermal MPhis. Furthermore, a specific role for TLR13 with respect to MPhi function is supported by the response to staphylococci, where TLR13 and UNC-93B limit the cytokine response in bone marrow-derived MPhis and microglia, but not in dermal MPhis. In summary, TLR13 is a critical and site-specific receptor in the single MPhi response to beta-hemolytic streptococci.
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