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

Summary

A fungal pump protein called Spf1 helps Candida albicans secrete toxins that damage the immune system during infection. When researchers deleted the SPF1 gene, the fungus could not effectively release these toxins, triggering a much weaker immune response and allowing infected mice to survive better. This discovery suggests that controlling this calcium pump could be a new strategy for treating serious fungal infections.

Background

Spf1 is a P-type ATPase calcium pump in Candida albicans that maintains calcium homeostasis and endoplasmic reticulum function. While Spf1 deficiency attenuates C. albicans virulence, its impact on host immune response during systemic infection remains unclear.

Objective

This study investigates the role of Spf1 in regulating endoplasmic reticulum-plasma membrane (ER-PM) contacts and its effects on virulence factor secretion and immune response during C. albicans systemic infection.

Results

SPF1 deletion reduced ER-PM contacts through decreased plasma membrane localization of tethering proteins Ist2 and Tcb1/3, resulting in reduced secretion of phospholipase, SAP, candidalysin, and Hwp1. This led to significantly decreased pro-inflammatory cytokine levels and marked reduction in kidney inflammation and immune cell infiltration in infected mice.

Conclusion

Spf1-governed ER-PM contacts regulate immune response during C. albicans infection. Controlling SPF1 expression and function offers a novel therapeutic strategy for treating fungal infections by modulating host immune response while reducing fungal virulence.
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