The pattern recognition receptors Nod1 and Nod2 account for neutrophil recruitment to the lungs of mice infected with Legionella pneumophila |
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Authors: | Mariana S. Frutuoso Juliana I. Hori Marcelo S.F. Pereira Djalma S.L. Junior Fabiane Sônego Koichi S. Kobayashi Richard A. Flavell Fernando Q. Cunha Dario S. Zamboni |
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Affiliation: | 1. Department of Cell Biology, University of São Paulo, School of Medicine of Ribeirão Preto, FMRP/USP, Ribeirão Preto, SP 14049-900, Brazil;2. Department of Pharmacology, University of São Paulo, School of Medicine of Ribeirão Preto, FMRP/USP, Ribeirão Preto, SP 14049-900. Brazil;3. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA;4. Department of Immunobiology, Yale University School of Medicine and Howard Hughes Medical Institute, New Haven, CT 06510, USA |
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Abstract: | 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. |
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