Aspartyl proteases target host actin nucleator complex protein to limit epithelial innate immunity
Year: 2024
Type: article
Abstract: Epithelial-immune cell communication is pivotal to control microbial infections. We show that glycosylphosphatidylinositol-linked aspartyl proteases (Yapsins) of the human opportunistic pathogenic yeast Candida glabrata (Cg) thwart epithelial cell (EC)-neutrophil signalling by targeting the EC protein, Arpc1B (actin nucleator Arp2/3 complex subunit), which leads to actin disassembly and impeded IL-8 secretion by ECs. Further, the diminished IL-8 secretion inhibits neutrophil migration, and protects Cg from the neutrophil-mediated killing. CgYapsin-dependent Arpc1B degradation requires Arginine-142 in Arpc1B, and leads to reduced Arpc1B-p38 MAPK interaction and downregulated p38 signalling. Consistently, Arpc1B or p38 deletion promotes survival of the Cg aspartyl protease-deficient mutant in ECs. Importantly, kidneys of the protease-deficient mutant-infected mice display elevated immune cell infiltration and cytokine secretion, implicating CgYapsins in immune response suppression in vivo. Besides delineating Cg-EC interplay, our results uncover a novel target, Arpc1B, that pathogens attack to constrain the host signalling networks, and link Arpc1B mechanistically with p38 activation.
Source: EMBO Reports
Authors: Sandip Patra, Rupinder Kaur
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,890
Awards: G1433807411, G1894350140, Delineating molecular mechanisms underlying Candida glabrata-host interaction: Role of metabolic and epigenetic reprogramming in immune evasion, Characterization of glycosylphosphatidylinositol-linked aspartyl proteases in Candida glabrata: role in pathogenicity, G3183646480, G7990789850
OpenAlex ID: W4402992278