In:
The Journal of Immunology, The American Association of Immunologists, Vol. 208, No. 1_Supplement ( 2022-05-01), p. 58.08-58.08
Abstract:
We recently discovered a role for Nod2 within T cells in controlling Th17-immunity, such that deletion of Nod2 exacerbated experimental autoimmune arthritis and uveitis. Protection against opportunistic Candida albicans infection relies on intact Th17-responses. Thus, we considered whether the T cell intrinsic Nod2 might control antifungal Th17 responses at the cost of increasing host susceptibility to autoimmunity. Nod2−/− mice infected with 105 (LD50) Candida albicans had increased survival and reduced fungal burden in the kidney within 24–72 h post-infection, suggesting a critical role for Nod2 in C. albicans immunity. Rag−/− mice reconstituted with Nod2fl/fl/CD4-cre CD4+ T cells and infected with C. albicans had decreased fungal burden compared to control CD4-Cre T cell recipients, and IL-17 depletion reverted the phenotype. After 48h infection, Nod2fl/fl/CD4-cre CD4+ T cells in the kidney had increased activation (CD69), increased proportion of T effector cells, and decreased Tregs compared to controls, suggesting endogenous Nod2 negatively regulates fungal-triggered Teff/Th17 cell responses. We next asked how Nod2 might function in SKG mice that are genetically susceptible to arthritis. Whereas Nod2−/− SKG mice developed an exacerbated form of arthritis compared to Nod2+/+ SKG controls, these same mice cleared C. albicans infection better than Nod2+/+ SKG mice. Cumulatively our data indicate a critical role for T cell intrinsic Nod2 in antifungal Th17 immunity. Given these studies we posit that human NOD2 genetic variants may offer enhanced ability to fight fungal infection via a T cell intrinsic mechanism, at the cost of triggering autoimmunity. Supported by grants from VA (CDA-2 IK2BX004523 and Merit I01BX002180) and NIH (R01 EY025250).
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.208.Supp.58.08
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2022
detail.hit.zdb_id:
1475085-5
