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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

NOD2-RIP2-Mediated Signaling Helps Shape Adaptive Immunity in Visceral Leishmaniasis

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Nascimento, Manuela S. L. ; Ferreira, Marcela D. ; Quirino, Gustavo F. S. ; Maruyama, Sandra R. ; Krishnaswamy, Jayendra K. ; Liu, Dong ; Berlink, Jonilson ; Fonseca, Denise M. ; Zamboni, Dario S. ; Carregaro, Vanessa ; Almeida, Roque P. ; Cunha, Thiago M. ; Eisenbarth, Stephanie S. ; Silva, Joao S.
Total Authors: 14
Document type: Journal article
Source: Journal of Infectious Diseases; v. 214, n. 11, p. 1647-1657, DEC 1 2016.
Web of Science Citations: 5

Interferon gamma (IFN-gamma) and interleukin 17A (IL-17A)-producing cells are described to be related to the protection against Leishmania infantum infection. How the immune system coordinates the balance between T-helper type 1 (Th1) and 17 (Th17) responses during visceral leishmaniasis (VL) is still unknown. Here, we combined transcriptional profiling, using RNA sequencing analysis of human samples, with an experimental model to show that Th17-related genes are suppressed and that Th1 signature genes are induced during human VL. The high amount of Th1 cells in VL was dependent on the NOD2-RIP2 signaling in dendritic cells, which was crucial for interleukin 12 production through the phosphorylation of MAPK. On the other hand, this pathway inhibits Th17 cells by limiting interleukin 23 production. As a consequence, Nod2(-/-) and Rip2(-/-) mice showed defects in Th1 responses and higher parasite loads as compared to WT mice. Together, the data demonstrate that the NOD2-RIP2 pathway is activated in murine and human VL and plays a role in shaping adaptive immunity toward a Th1 profile. (AU)

FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
Grantee:Fernando de Queiroz Cunha
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC