Department of Microbiology and Immunology, Indiana University School of Medicine-Terre Haute, Terre Haute, IN.
Department of Biology, Indiana State University, Terre Haute, IN.
Immunohorizons. 2021 Dec 22;5(12):983-993. doi: 10.4049/immunohorizons.2100092.
is a ubiquitous mold associated with the development of pulmonary diseases that include invasive pulmonary aspergillosis (IPA), an often fatal opportunistic infection. FIBCD1 is a transmembrane endocytic membrane receptor widely expressed on human epithelium. Although FIBCD1 was previously shown to bind chitin, modulate fungal colonization of the gut, and inhibit intestinal inflammation, the role of FIBCD1 in the context of lung fungal infection remains unknown. In this study, we observed that mortality, fungal burden, and tissue histopathology were decreased in the absence of FIBCD1 in murine IPA. Quantitative RT-PCR analyses demonstrated decreased inflammatory cytokines in the lungs of neutrophil-depleted FIBCD1 mice with IPA, when compared with wild-type controls. In contrast, inflammatory cytokines were increased in immune-competent FIBCD1 mice after fungal aspiration, suggesting that the presence of neutrophils is associated with cytokine modulation. In contrast to the clear IPA phenotype, FIBCD1 mice with systemic infection or bleomycin-induced lung injury exhibited similar morbidity and mortality when compared with their wild-type counterparts. Thus, our study identifies a detrimental role of FIBCD1 in IPA.
是一种普遍存在的霉菌，与肺部疾病的发展有关，包括侵袭性肺曲霉病（IPA），这是一种常致命的机会性感染。FIBCD1 是一种广泛表达于人上皮细胞的跨膜内吞膜受体。尽管先前已经表明 FIBCD1 可以结合几丁质、调节肠道真菌定植，并抑制肠道炎症，但 FIBCD1 在肺部真菌感染背景下的作用仍不清楚。在这项研究中，我们观察到在 IPA 中缺乏 FIBCD1 的情况下，小鼠的死亡率、真菌负荷和组织组织病理学均降低。与野生型对照相比，中性粒细胞耗竭的 FIBCD1 IPA 小鼠的肺部炎症细胞因子减少。相比之下，在真菌吸入后免疫功能正常的 FIBCD1 小鼠中炎症细胞因子增加，这表明中性粒细胞的存在与细胞因子的调节有关。与明确的 IPA 表型相反，全身性感染或博来霉素诱导的肺损伤的 FIBCD1 小鼠与野生型对照相比，发病率和死亡率相似。因此，我们的研究确定了 FIBCD1 在 IPA 中的有害作用。
