The pattern recognition receptors Nod1 and Nod2 account for neutrophil recruitment to the lungs of mice infected with Legionella pneumophila

Autor(es)

Frutuoso, Mariana S. ^[1] ; Hori, Juliana I. ^[1] ; Pereira, Marcelo S. F. ^[1] ; Junior, Djalma S. L. ^[1] ; Sonego, Fabiane ^[2] ; Kobayashi, Koichi S. ^{[3, 4]} ; Flavell, Richard A. ^{[5, 6]} ; Cunha, Fernando Q. ^[2] ; Zamboni, Dario S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Cell Biol, FMRP USP, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, FMRP USP, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 - USA

^[4] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 - USA

^[5] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06510 - USA

^[6] Howard Hughes Med Inst, New Haven, CT 06510 - USA

• Tipo de documento: Artigo Científico
• Fonte: Microbes and Infection; v. 12, n. 11, p. 819-827, OCT 2010.
• Citações Web of Science: 58

Resumo

The intracellular bacterium Legionella pneumophila induces a severe form of pneumonia called Legionnaires diseases, which is characterized by a strong neutrophil (NE) infiltrate to the lungs of infected individuals. Although the participation of pattern recognition receptors, such as Toll-like receptors, was recently demonstrated, there is no information on the role of nod-like receptors (NLRs) for bacterial recognition in vivo and for NE recruitment to the lungs. Here, we employed a murine model of Legionnaires disease to evaluate host and bacterial factors involved in NE recruitment to the mice lungs. We found that L. pneumophila type four secretion system, known as Dot/Icm, was required for NE recruitment as dot/icm mutants fail to trigger NE recruitment in a process independent of bacterial multiplication. By using mice deficient for Nod1, Nod2, and Rip2, we found that these receptors accounted for NE recruitment to the lungs of infected mice. In addition, Rip2-dependent responses were important for cytokine production and bacterial clearance. Collectively, these studies show that Nod1, Nod2, and Rip2 account for generation of innate immune responses in vivo, which are important for NE recruitment and bacterial clearance in a murine model of Legionnaires diseases. (C) 2010 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. (AU)

• Processo FAPESP: 06/52867-4 - Reconhecimento de patógenos bacterianos por receptores intracelulares e sua importância no controle da infecção microbiana
• Beneficiário: Dario Simões Zamboni
• Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores