Aspartyl proteases in Candida glabrata are required for suppression of the host innate immune response

The Journal of Biological Chemistry
Mubashshir RasheedRupinder Kaur

Abstract

A family of 11 cell surface-associated aspartyl proteases (CgYps1-11), also referred as yapsins, is a key virulence factor in the pathogenic yeast Candida glabrata However, the mechanism by which CgYapsins modulate immune response and facilitate survival in the mammalian host remains to be identified. Here, using RNA-Seq analysis, we report that genes involved in cell wall metabolism are differentially regulated in the Cgyps1-11Δ mutant. Consistently, the mutant contained lower β-glucan and mannan levels and exhibited increased chitin content in the cell wall. As cell wall components are known to regulate the innate immune response, we next determined the macrophage transcriptional response to C. glabrata infection and observed differential expression of genes implicated in inflammation, chemotaxis, ion transport, and the tumor necrosis factor signaling cascade. Importantly, the Cgyps1-11Δ mutant evoked a different immune response, resulting in an enhanced release of the pro-inflammatory cytokine IL-1β in THP-1 macrophages. Further, Cgyps1-11Δ-induced IL-1β production adversely affected intracellular proliferation of co-infected WT cells and depended on activation of spleen tyrosine kinase (Syk) signaling in the host cells. Acc...Continue Reading

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Citations

Aug 23, 2019·MSphere·Dhirendra Kumar SinghAttila Gácser
Jul 17, 2020·Expert Review of Anti-infective Therapy·Mubashshir RasheedRupinder Kaur
Feb 2, 2019·Microorganisms·Kundan KumarRupinder Kaur
Feb 9, 2021·The Biochemical Journal·Bruna GonçalvesSónia Silva
Oct 18, 2019·Journal of Proteome Research·Mubashshir RasheedRupinder Kaur

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Datasets Mentioned

BETA
SUB1954295
SRP090201
PRJNA343588
GSE86176

Methods Mentioned

BETA
RNA-Seq
GTPase
ELISArray
ELISA
PCR
PMA
Feature Extraction
scraping
flow cytometry

Software Mentioned

Geneious Basic
CUFFLINKS
FlowJo
Slim Mapper
GraphPad Prism
Agilent Feature Extraction
ImageJ
DAVID

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