NOD2-RIP2-mediated signaling helps shape adaptive immunity in visceral leishmaniasis

Manuela S.L. Nascimento, Marcela D. Ferreira, Gustavo F.S. Quirino, Sandra R. Maruyama, Jayendra K. Krishnaswamy, Dong Liu, Jonilson Berlink, Denise M. Fonseca, Dario S. Zamboni, Vanessa Carregaro, Roque P. Almeida, Thiago M. Cunha, Stephanie S. Eisenbarth, João S. Silva*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Interferon γ (IFN-γ) 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.

Original languageEnglish (US)
Pages (from-to)1647-1657
Number of pages11
JournalJournal of Infectious Diseases
Volume214
Issue number11
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

Keywords

  • Adaptive immunity
  • Dendritic cells
  • Leishmania infatum
  • NOD2
  • RIP2
  • Visceral leishmaniasis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'NOD2-RIP2-mediated signaling helps shape adaptive immunity in visceral leishmaniasis'. Together they form a unique fingerprint.

Cite this