The RIG-I-like helicase receptor MDA5 (IFIH1) is involved in the host defense against Candida infections.

Eur J Clin Microbiol Infect Dis 2015 May 13;34(5):963-974. Epub 2015 Jan 13.

Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.

The induction of host defense against Candida species is initiated by recognition of the fungi by pattern recognition receptors and activation of downstream pathways that produce inflammatory mediators essential for infection clearance. In this study, we present complementary evidence based on transcriptome analysis, genetics, and immunological studies in knockout mice and humans that the cytosolic RIG-I-like receptor MDA5 (IFIH1) has an important role in the host defense against C. albicans. Firstly, IFIH1 expression in macrophages is specifically induced by invasive C. albicans hyphae, and patients suffering from chronic mucocutaneous candidiasis (CMC) express lower levels of MDA5 than healthy controls. Secondly, there is a strong association between missense variants in the IFIH1 gene (rs1990760 and rs3747517) and susceptibility to systemic Candida infections. Thirdly, cells from Mda5 knockout mice and human peripheral blood mononuclear cells (PBMCs) with different IFIH1 genotypes display an altered cytokine response to C. albicans. These data strongly suggest that MDA5 is involved in immune responses to Candida infection. As a receptor for viral RNA, MDA5 until now has been linked to antiviral host defense, but these novel studies show unexpected effects in antifungal immunity as well. Future studies are warranted to explore the potential of MDA5 as a novel target for immunotherapeutic strategies.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10096-014-2309-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084092PMC
May 2015
27 Reads

Publication Analysis

Top Keywords

host defense
16
knockout mice
8
candida infections
8
defense candida
8
receptor mda5
8
mda5 ifih1
8
mda5
7
ifih1
5
mda5 linked
4
patients suffering
4
hyphae patients
4
mucocutaneous candidiasis
4
chronic mucocutaneous
4
viral rna
4
suffering chronic
4
rna mda5
4
cmc express
4
levels mda5
4
mda5 healthy
4
infection receptor
4

References

(Supplied by CrossRef)

O Gudlaugsson et al.
Clin Infect Dis 2003

H Wisplinghoff et al.
Clin Infect Dis 2004

LG Miller et al.
Clin Infect Dis 2001

TE Zaoutis et al.
Clin Infect Dis 2005

SP Smeekens et al.
EMBO Mol Med 2013

TS Plantinga et al.
J Infect Dis 2012

EO Glocker et al.
N Engl J Med 2009

FL Veerdonk van de et al.
N Engl J Med 2011

L Liu et al.
J Exp Med 2011

O Babula et al.
Clin Infect Dis 2005

SP Smeekens et al.
Nat Commun 2013

Similar Publications