T cell-intrinsic role of Nod2 in promoting type 1 immunity to Toxoplasma gondii.
Nod2 belongs to the nucleotide-binding oligomerization domain receptor (NLR) family of proteins, which function as intracellular pathogen sensors in innate immune cells. Nod2 deficiency results in an impaired immune response to bacterial pathogens. However, how this protein promotes host defense against intracellular parasites is unknown. Here we found that Nod2(-/-) mice had less clearance of Toxoplasma gondii and lower interferon-gamma (IFN-gamma) production. Reconstitution of T cell-deficient mice with Nod2(-/-) T cells followed by T. gondii infection demonstrated a T cell-intrinsic defect. Nod2(-/-) CD4(+) T cells had poor helper T cell differentiation, which was associated with impaired production of interleukin 2 (IL-2) and nuclear accumulation of the transcription factor subunit c-Rel. Our data demonstrate a T cell-intrinsic role for Nod2 signaling that is critical for host defense against T. gondii.
Shaw
Michael H
MH
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Reimer
Thornik
T
Sánchez-Valdepeñas
Carmen
C
Warner
Neil
N
Kim
Yun-Gi
YG
Fresno
Manuel
M
Nuñez
Gabriel
G
D000818:Animals; D002454:Cell Differentiation; D003092:Colitis / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D053473:Nod2 Signaling Adaptor Protein / Q000172:deficiency / Q000276:immunology*; D015398:Signal Transduction; D015996:Survival Rate; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology* / Q000378:metabolism
D007376:Interleukin-2; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D007371:Interferon-gamma