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Nod2-deficient CD4+ T cells protect against Candida albicans infection
Nucleotide-binding oligomerization domain-containing protein 2 (Nod2) is a pattern recognition receptor known to promote anti-bacterial immunity yet its function in fungal disease is less understood. Here we sought to investigate the role of Nod2 in regulating fungal infection. Our results demonstra...
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Published in: | The Journal of immunology (1950) 2021-05, Vol.206 (1_Supplement), p.16-16.20 |
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Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | Nucleotide-binding oligomerization domain-containing protein 2 (Nod2) is a pattern recognition receptor known to promote anti-bacterial immunity yet its function in fungal disease is less understood. Here we sought to investigate the role of Nod2 in regulating fungal infection. Our results demonstrate that Nod2−/− mice infected with 105 (LD50) Candida albicans had increased survival and reduced kidney pathology compared to WT mice, indicating an important role for Nod2-deficiency in protection against infection. In corroboration, Nod2−/− mice had increased fungal clearance in the kidney within 24–72 h post-infection. T cell-deficient Rag−/− or Nod2−/− Rag−/− mice infected with C. albicans had similar fungal burdens, indicating a cellular role for Nod2 outside of innate and non-hematopoietic cells. In support, Nod2−/− mouse kidneys had increased frequencies of CD4+ T cells 48h post-infection, indicating a potential protective function for Nod2−/− T cells. To evaluate a putative T cell-intrinsic function of Nod2 we infected Rag1−/− mice reconstituted with CD4+ T cells from conditional knockout mice deficient in Nod2 in CD4+ T cells (Nod2fl/fl/CD4-cre) or control mice (CD4-cre). Mice harboring CD4+ T cells from Nod2fl/fl/CD4-cre mice had decreased fungal burden within 48 h and increased Th17 cells in the kidneys akin to the global Nod2−/− mice. Protection conferred by Nod2-deficient CD4+ T cells was abrogated by neutralization of IL-17, indicating the functional importance of the Nod2/IL-17 response in CD4+ T cells in C. albicans pathogenesis. Cumulatively, our data suggest that in opposition to the known protective role of Nod2 in bacterial infections, T cell-intrinsic Nod2 promotes fungal infection. |
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ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.206.Supp.16.20 |