The phytosphingosine-CD300b interaction promotes zymosan-induced, nitric oxide–dependent neutrophil recruitment

Autor: Jiro Kitaura, Hiromichi Yamada, Ayako Takamori, Toshiaki Shimizu, Ayako Kaitani, Yoshinori Yamanishi, Mariko Takahashi, Hideoki Ogawa, Toshio Kitamura, Shino Uchida, Toshihiro Matsukawa, Masakazu Nagamine, Makoto Urai, Tomoaki Ando, Ko Okumura, Akie Maehara, Kumi Izawa, Masamichi Isobe, Yuki Kinjo
Rok vydání: 2019
Předmět:
Zdroj: Science Signaling. 12
ISSN: 1937-9145
1945-0877
DOI: 10.1126/scisignal.aar5514
Popis: Zymosan is a glucan that is a component of the yeast cell wall. Here, we determined the mechanisms underlying the zymosan-induced accumulation of neutrophils in mice. Loss of the receptor CD300b reduced the number of neutrophils recruited to dorsal air pouches in response to zymosan, but not in response to lipopolysaccharide (LPS), a bacterial membrane component recognized by Toll-like receptor 4 (TLR4). An inhibitor of nitric oxide (NO) synthesis reduced the number of neutrophils in the zymosan-treated air pouches of wild-type mice to an amount comparable to that in CD300b-/- mice. Treatment with clodronate liposomes decreased the number of NO-producing, CD300b+ inflammatory dendritic cells (DCs) in wild-type mice, thus decreasing NO production and neutrophil recruitment. Similarly, CD300b deficiency decreased the NO-dependent recruitment of neutrophils to zymosan-treated joint cavities, thus ameliorating subsequent arthritis. We identified phytosphingosine, a lipid component of zymosan, as a potential ligand of CD300b. Phytosphingosine stimulated NO production in inflammatory DCs and promoted neutrophil recruitment in a CD300b-dependent manner. Together, these results suggest that the phytosphingosine-CD300b interaction promotes zymosan-dependent neutrophil accumulation by inducing NO production by inflammatory DCs and that CD300b may contribute to antifungal immunity.
Databáze: OpenAIRE