Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, CA 90502, USA; Institute for Infection and Immunity, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, CA 90502, USA; Institute for Infection and Immunity, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Cell Rep. 2019 Jul 9;28(2):423-433.e5. doi: 10.1016/j.celrep.2019.06.020.
During oropharyngeal candidiasis (OPC), Candida albicans proliferates and invades the superficial oral epithelium. Ephrin type-A receptor 2 (EphA2) functions as an oral epithelial cell β-glucan receptor that triggers the production of proinflammatory mediators in response to fungal infection. Because EphA2 is also expressed by neutrophils, we investigated its role in neutrophil candidacidal activity during OPC. We found that EphA2 on stromal cells is required for the accumulation of phagocytes in the oral mucosa of mice with OPC. EphA2 on neutrophils is also central to host defense against OPC. The interaction of neutrophil EphA2 with serum-opsonized C. albicans yeast activates the MEK-ERK signaling pathway, leading to NADPH subunit p47 site-specific phospho-priming. This priming increases intracellular reactive oxygen species production and enhances fungal killing. Thus, in neutrophils, EphA2 serves as a receptor for β-glucans that augments Fcγ receptor-mediated antifungal activity and controls early fungal proliferation during OPC.
在口咽念珠菌病（OPC）期间，白念珠菌增殖并侵袭口腔上皮的浅层。Ephrin 型-A 受体 2（EphA2）作为口腔上皮细胞 β-葡聚糖受体发挥作用，可在真菌感染时触发促炎介质的产生。由于 EphA2 也由中性粒细胞表达，因此我们研究了其在 OPC 期间中性粒细胞杀念珠菌活性中的作用。我们发现 OPC 小鼠口腔黏膜中吞噬细胞的聚集需要基质细胞上的 EphA2。中性粒细胞上的 EphA2 也是宿主防御 OPC 的核心。中性粒细胞 EphA2 与血清调理的白念珠菌酵母的相互作用激活了 MEK-ERK 信号通路，导致 NADPH 亚基 p47 位点特异性磷酸化引发。这种引发增加了细胞内活性氧的产生，并增强了真菌杀伤作用。因此，在中性粒细胞中，EphA2 作为β-葡聚糖的受体，增强了 Fcγ 受体介导的抗真菌活性，并控制 OPC 期间早期真菌的增殖。
