| First Author | Matsumura T | Year | 2019 |
| Journal | Cell Rep | Volume | 27 |
| Issue | 2 | Pages | 561-571.e6 |
| PubMed ID | 30970258 | Mgi Jnum | J:281233 |
| Mgi Id | MGI:6377733 | Doi | 10.1016/j.celrep.2019.03.056 |
| Citation | Matsumura T, et al. (2019) Sequential Sensing by TLR2 and Mincle Directs Immature Myeloid Cells to Protect against Invasive Group A Streptococcal Infection in Mice. Cell Rep 27(2):561-571.e6 |
| abstractText | Severe invasive group A Streptococcus (GAS) infection evades anti-bacterial immunity by attenuating the cellular components of innate immune responses. However, this loss of protection is compensated for by interferon (IFN)-gamma-producing immature myeloid cells (gammaIMCs), which are selectively recruited upon severe invasive GAS infection in mice. Here, we demonstrate that gammaIMCs provide this IFN-gamma-mediated protection by sequentially sensing GAS through two distinct pattern recognition receptors. In a mouse model, GAS is initially recognized by Toll-like receptor 2 (TLR2), which promptly induces interleukin (IL)-6 production in gammaIMCs. gammaIMC-derived IL-6 promotes the upregulation of a recently identified GAS-sensing receptor, macrophage-inducible C-type lectin (Mincle), in an autocrine or paracrine manner. Notably, blockade of gammaIMC-derived IL-6 abrogates Mincle expression, downstream IFN-gamma production, and gammaIMC-mediated protection against severe invasive GAS infection. Thus, gammaIMCs regulate host protective immunity against severe invasive GAS infection via a TLR2-IL-6-Mincle axis. |
