Sialophorin is an essential host element for immunity against fungal pneumonia

Abstract

Abstract Invasive fungal infections (IFI) are emerging diseases accounting for 1.7 million deaths and 150 million life-threatening diseases worldwide annually. The increased population of immunocompromised individuals and lack of arsenal of antifungal drugs necessitate an understanding of mechanisms of host-pathogen interactions to define new preventive and therapeutic targets. Here, we show that sialophorin (CD43), a transmembrane glycoprotein, is necessary to mediate protective immunity against primary pulmonary fungal infection. Using a mouse model of lethal fungal infection with Blastomyces dermatitidis, we learned that ablation of sialophorin enhanced the severity of disease, pathology, and accelerated death. At the cellular level, alveolar macrophages, one of the first lines of innate cellular barriers, were blunted in the absence of sialophorin. Additionally, sialophorin deficiency truncated the numbers of inflammatory monocytes, CD103+ DC, and interstitial macrophages. Surprisingly, sialophorin was dispensable for neutrophils. Despite sialophorin implication, the defect seen under sialophorin deficiency was independent of the cell trafficking. Finally, we uncovered that sialophorin augmented IL-17A responses from innate lymphoid cells. Collectively, we show that sialophorin is an essential host element for innate immunity against pulmonary fungal infection and can be an immune target for the control of fungal infections. Funding support: Innovation Award by the American Lung Association to SGN. Supported by Innovation Award by the American Lung Association to SGN.