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Crucial role for T cell-intrinsic IL-18R-MyD88 signaling in cognate immune response to intracellular parasite infection

  1. Ana-Carolina Oliveira
  2. João Francisco Gomes-Neto
  3. Carlos-Henrique Dantas Barbosa
  4. Alessandra Granato
  5. Bernardo S Reis
  6. Bruno Maia Santos
  7. Rita Fucs
  8. Fábio B Canto
  9. Helder I Nakaya
  10. Alberto Nóbrega
  11. Maria Bellio Is a corresponding author
  1. Universidade Federal do Rio de Janeiro (UFRJ), Brazil
  2. The Rockefeller University, United States
  3. Universidade Federal Fluminense (UFF), Brazil
  4. Universidade de São Paulo (USP), Brazil
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Cite as: eLife 2017;6:e30883 doi: 10.7554/eLife.30883

Abstract

MyD88 is the main adaptor molecule for TLR and IL-1R family members. Here, we demonstrated that T-cell intrinsic MyD88 signaling is required for proliferation, protection from apoptosis and expression of activation/memory genes during infection with the intracellular parasite Trypanosoma cruzi, as evidenced by transcriptome and cytometry analyses in mixed bone-marrow (BM) chimeras. The lack of direct IL-18R signaling in T cells, but not of IL-1R, phenocopied the absence of the MyD88 pathway, indicating that IL-18R is a critical MyD88-upstream pathway involved in the establishment of the Th1 response against an in vivo infection, a presently controvert subject. Accordingly, Il18r1-/- mice display lower levels of Th1 cells and are highly susceptible to infection, but can be rescued from mortality by the adoptive transfer of WT CD4+ T cells. Our findings establish the T-cell intrinsic IL-18R/MyD88 pathway as a crucial element for induction of cognate Th1 responses against an important human pathogen.

Article and author information

Author details

  1. Ana-Carolina Oliveira

    Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  2. João Francisco Gomes-Neto

    Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  3. Carlos-Henrique Dantas Barbosa

    Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  4. Alessandra Granato

    Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  5. Bernardo S Reis

    The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Bruno Maia Santos

    Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  7. Rita Fucs

    Instituto de Biologia, Universidade Federal Fluminense (UFF), Niteroi, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  8. Fábio B Canto

    Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  9. Helder I Nakaya

    Faculdade de Ciências Farmacêuticas, Universidade de São Paulo (USP), Sao Paulo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  10. Alberto Nóbrega

    Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  11. Maria Bellio

    Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
    For correspondence
    mariabellioufrj@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-3360-2740

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico (402932/2012-9)

  • Maria Bellio

Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (103.078/2011 and 110.168/2013)

  • Maria Bellio

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Experiments were conducted in strict accordance with guidelines of the Animal Care and Use Committee of the Federal University of Rio de Janeiro (Comitê de Ética do Centro de Ciências da Saúde CEUA-CCS/UFRJ). Procedures and animal protocols were approved by CEUA-CCS/UFRJ license n.: IMPPG022. Every effort was made to minimize suffering.

Reviewing Editor

  1. Urszula Krzych, Reviewing Editor, Walter Reed Army Institute of Research, United States

Publication history

  1. Received: July 30, 2017
  2. Accepted: September 12, 2017
  3. Accepted Manuscript published: September 12, 2017 (version 1)

Copyright

© 2017, Oliveira et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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