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- Title
NFATc1 Mediates Toll-Like Receptor-Independent Innate Immune Responses during Trypanosoma cruzi Infection.
- Authors
Kayama, Hisako; Koga, Ritsuko; Atarashi, Koji; Okuyama, Megumi; Kimura, Taishi; Mak, Tak W.; Uematsu, Satoshi; Akira, Shizuo; Takayanagi, Hiroshi; Honda, Kenya; Yamamoto, Masahiro; Takeda, Kiyoshi
- Abstract
Host defense against the intracellular protozoan parasite Trypanosoma cruzi depends on Toll-like receptor (TLR)-dependent innate immune responses. Recent studies also suggest the presence of TLR-independent responses to several microorganisms, such as viruses, bacteria, and fungi. However, the TLR-independent responses to protozoa remain unclear. Here, we demonstrate a novel TLR-independent innate response pathway to T. cruzi. Myd88-/-Trif-/- mice lacking TLR signaling showed normal T. cruzi-induced Th1 responses and maturation of dendritic cells (DCs), despite high sensitivity to the infection. IFN-γ was normally induced in T. cruzi-infected Myd88-/-Trif-/- innate immune cells, and further was responsible for the TLR-independent Th1 responses and DC maturation after T. cruzi infection. T. cruzi infection induced elevation of the intracellular Ca2+ level. Furthermore, T. cruzi-induced IFN-γ expression was blocked by inhibition of Ca2+ signaling. NFATc1, which plays a pivotal role in Ca2+ signaling in lymphocytes, was activated in T. cruzi-infected Myd88-/-Trif-/- innate immune cells. T. cruzi-infected Nfatc1-/- fetal liver DCs were impaired in IFN-γ production and DC maturation. These results demonstrate that NFATc1 mediates TLR-independent innate immune responses in T. cruzi infection.
- Subjects
PARASITIC diseases; PROTOZOAN diseases; TRYPANOSOMA cruzi; IMMUNE response; PATHOGENIC protozoa; PATHOGENIC microorganisms; DENDRITIC cells
- Publication
PLoS Pathogens, 2009, Vol 5, Issue 7, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1000514