The P-type calcium pump Spf1 regulates immune response by maintenance of the endoplasmic reticulum-plasma membrane contacts during <i>Candida albicans</i> systemic infection

Spf1 is an important P-type ATPase in <i>Candida albicans</i>, which functions as an endoplasmic reticulum calcium pump to maintain calcium homoeostasis. The deficiency of Spf1 attenuates the virulence of <i>C. albicans</i>. However, its impact on immune response remains to be investigated. This study discovered that deletion of <i>SPF1</i> resulted in a reduction of endoplasmic reticulum-plasma membrane contacts, an important structure mediating material and information exchange. This effect was attributed to the reduced plasma membrane localisation of the crucial endoplasmic reticulum-plasma membrane tethering proteins Ist2 and Tcb1/3. The reduction of the contacts led to a decrease in secretion of the virulence factors phospholipase, secreted aspartyl protease (SAP), candidalysin, and the cell wall-anchored protein Hwp1 during infection. Immunofluorescence staining and quantitative PCR assays further showed that the <i>SPF1</i> deletion led to a remarkable decrease in the levels of pro-inflammatory cytokines, suggesting the alleviation of the fungus-induced inflammatory response. Ultimately, the regulatory role of Spf1 in immune response significantly weakened the infectivity of <i>C. albicans</i>, and increased the survival rate of the hosts. This finding elucidated the role of fungal calcium pump-governed endoplasmic reticulum-plasma membrane contacts in regulation of immune response. It also makes it possible to regulate the host's immune response via control of <i>SPF1</i> expression and functions, providing a theoretical basis for treating fungal infections.