T cell–intrinsic role of Nod2 in promoting type 1 immunity to Toxoplasma gondii
T cell–intrinsic role of Nod2 in promoting type 1 immunity to Toxoplasma gondii
Shaw MH, et al. 2009. Nat. immunol. 10(12), 1267-1274.
Speaker: Yu-Cheng Lin (林祐丞) Time: 14:00~15:00, April 28, 2010
Commentator: Pin Ling (凌斌 老師) Place: Room 601
Abstract:
Nods, including Nod1 and Nod2, belong to nucleotide-binding oligomerization domain (Nod)-like receptor (NLR) family, which function as intracellular pattern-recognition sensors by detecting microbial products. The detection of bacteria by Nods is well studied, but the role of Nod proteins in host defense against intracellular parasites is unclear. Toxoplasma gondii is an intracellular protozoan pathogen that wildly spreads in immuno-compromised hosts and infects various cells. T. gondii infection would induce protectively cellular immunity mediated by interleukin-12 (IL-12) and interferon-γ (IFN-γ) derived from natural killer (NK) cells and T helper type 1 (TH1) immune response【1】. Previous studies showed that extracellular T. gondii could be recognized by the Toll-like receptors (TLRs), TLR11 which detects profiling-like protein of T. gondii【2】and TLR2 which detects other ligands of T. gondii【3】, expressed on dendritic cells (DCs) to promote pro-inflammation response. However, when T. gondii invade in host cells, they would form, reside and replicate in a nonfusogenic parasitophorous vacuole in the cytoplasm. Therefore, Shaw et al. would like to determine if the host cells uses an intracellular detection system, such as Nod proteins, to sense intracellular parasites. They found that only Nod2-/- but not other NLR-deficient mice had less clearance of T. gondii and lower IFN-γ production. Reconstitution of T cell- deficient mice with Nod2-/- T cells demonstrated a T cell-intrinsic defect. Moreover, Nod2 deficiency influences TH cells signaling, proliferation and differentiation, which were associated with impaired production of interleukin 2 (IL-2) and nuclear accumulation of transcription factor subunit c-Rel. Together these finding, They suggest that Nod2 provides a T cell-intrinsic signal that is necessary for generating protective TH1 immunity to T. gondii, and they also challenge the current dogma that Nod2 plays a role in innate immune to recognize bacterial motif by showing Nod2 providing T cell-intrinsic signal without ligand recognition as we know.
References:
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3. Mun HS, et al. 2003. TLR2 as an essential molecule for protective immunity against Toxoplasma gondii infection. Int. Immunol. 15, 1081–1087.