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.

酵母聚糖是一种葡聚糖，是酵母细胞壁的组成部分。在这里，我们确定了zymosan诱导小鼠中性粒细胞积累的潜在机制。受体CD300b的丢失减少了响应酵母聚糖而不是响应脂多糖（LPS）（被Toll样受体4（TLR4）识别的细菌膜成分）而募集到背部气袋的中性粒细胞的数量。一氧化氮（NO）合成抑制剂可将经野生型小鼠经酵母聚糖处理的气袋中的中性粒细胞数量减少至与CD300b ^-/-小鼠相当的数量。氯膦酸盐脂质体治疗减少了NO产生的数量，CD300b ⁺在野生型小鼠体内会产生炎性树突状细胞（DC），从而减少NO的产生和中性粒细胞的募集。同样，CD300b缺乏症减少了嗜中性粒细胞向依赖酵母聚糖处理的关节腔的NO依赖性募集，从而减轻了随后的关节炎。我们确定了植物鞘氨醇，一种酵母聚糖的脂质成分，作为CD300b的潜在配体。植物鞘氨醇可刺激CD产生NO，并以CD300b依赖性方式促进嗜中性白细胞的募集。在一起，这些结果表明植物鞘氨醇-CD300b相互作用通过诱导炎性DC产生NO来促进酵母聚糖依赖性中性粒细胞的积累，并且CD300b可能有助于抗真菌免疫。