Involvement of the NLRP3 inflammasome in innate and humoral adaptive immune responses to fungal beta-glucan.
Fungal beta-glucan, such as curdlan, triggers antifungal innate immune responses as well as shaping adaptive immune responses. In this study, we identified a key pathway that couples curdlan to immune responses. Curdlan promoted the production of the proinflammatory cytokine IL-1beta by dendritic cells and macrophages through the NLRP3 inflammasome. Stimulation with Candida albicans and Saccharomyces cerevisiae also triggered the NLRP3 inflammasome-mediated IL-1beta production. In vivo, NLRP3 was required for efficient Ag-specific Ab production when curdlan was used as an adjuvant, whereas it was dispensable for the induction of Th1 and Th17 cell differentiation. Furthermore, stimulation of purified B cells with curdlan-induced CD69 up-regulation and IgM production while stimulation with other NLRP3 inflammasome activators, such as silica and aluminum salt, did not. Notably, this induction required NLRP3 but was independent of Toll-like receptor and IL-1 receptor family signaling, suggesting the presence of NLRP3-dependent and IL-1 receptor family independent mechanisms in B cells responsible for Ab responses. Collectively, these findings reveal a critical role for the NLRP3 inflammasome in the regulation of antifungal innate immune responses as well as B cell activation.
Kumar
Himanshu
H
Laboratory of Host Defense.
Kumagai
Yutaro
Y
Tsuchida
Tetsuo
T
Koenig
Paul A
PA
Satoh
Takashi
T
Guo
Zijin
Z
Jang
Myoung Ho
MH
Saitoh
Tatsuya
T
Akira
Shizuo
S
Kawai
Taro
T
D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D000906:Antibodies / Q000097:blood; D000908:Antibodies, Fungal / Q000096:biosynthesis / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology / Q000382:microbiology; D002176:Candida albicans / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012441:Saccharomyces cerevisiae / Q000276:immunology; D047071:beta-Glucans / Q000008:administration & dosage* / Q000276:immunology*
D000906:Antibodies; D000908:Antibodies, Fungal; D002352:Carrier Proteins; D018836:Inflammation Mediators; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D047071:beta-Glucans; C038459:curdlan