| Autor: |
Takayuki Matsumura, Tadayoshi Ikebe, Koji Arikawa, Masahito Hosokawa, Michio Aiko, Aoi Iguchi, Ikuko Togashi, Sayaka Kai, Sakiko Ohara, Naoya Ohara, Makoto Ohnishi, Haruo Watanabe, Kazuo Kobayashi, Haruko Takeyama, Sho Yamasaki, Yoshimasa Takahashi, Manabu Ato |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 27, Iss 2, Pp 561-571.e6 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2019.03.056 |
| Popis: |
Summary: 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)-γ-producing immature myeloid cells (γIMCs), which are selectively recruited upon severe invasive GAS infection in mice. Here, we demonstrate that γIMCs provide this IFN-γ-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 γIMCs. γIMC-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 γIMC-derived IL-6 abrogates Mincle expression, downstream IFN-γ production, and γIMC-mediated protection against severe invasive GAS infection. Thus, γIMCs regulate host protective immunity against severe invasive GAS infection via a TLR2–IL-6–Mincle axis. : Matsumura et al. show that γIMCs sequentially sense group A Streptococcus (GAS) through TLR2 and Mincle. Specifically, TLR2-triggered production of IL-6 functions as an intermediate that amplifies Mincle expression to maximize host protection through IFN-γ production. The sequential sensing is a distinct feature in γIMCs following severe invasive GAS infection. Keywords: group A Streptococcus infections, immature myeloid cells, Toll-like receptors, C-type lectin receptors, cytokines |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
