Cutting edge: Nlrp10 is essential for protective antifungal adaptive immunity against Candida albicans.
Nucleotide-binding domain leucine-rich repeat containing receptors (NLRs) are cytosolic receptors that initiate immune responses to sterile and infectious insults to the host. Studies demonstrated that Nlrp3 is critical for the control of Candida albicans infections and in the generation of antifungal Th17 responses. In this article, we show that the NLR family member Nlrp10 also plays a unique role in the control of disseminated C. albicans infection in vivo. Nlrp10-deficient mice had increased susceptibility to disseminated candidiasis, as indicated by decreased survival and increased fungal burdens. In contrast to Nlrp3, Nlrp10 deficiency did not affect innate proinflammatory cytokine production from macrophages and dendritic cells challenged with C. albicans. However, Nlrp10-deficient mice displayed a profound defect in Candida-specific Th1 and Th17 responses. These results demonstrate a novel role for Nlrp10 in the generation of adaptive immune responses to fungal infection.
Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Sophie
S
Joly
Stephanie C
SC
Eisenbarth
Alicia K
AK
Olivier
Adam
A
Williams
Daniel H
DH
Kaplan
Suzanne L
SL
Cassel
Richard A
RA
Flavell
Fayyaz S
FS
Sutterwala
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D007111:Immunity, Cellular; D007113:Immunity, Innate / Q000235:genetics; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D016207:Cytokines; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C572764:NLRP10 protein, mouse; C492716:Nlrp3 protein, mouse