title: MyD88-, but not Nod1- and/or Nod2-deficient mice, show increased susceptibility to polymicrobial sepsis due to impaired local inflammatory response.
abstract: Pathogen recognition and triggering of the inflammatory response following infection in mammals depend mainly on Toll-like and Nod-like receptors. Here, we evaluated the role of Nod1, Nod2 and MyD88-dependent signaling in the chemokine production and neutrophil recruitment to the infectious site during sepsis induced by cecal ligation and puncture (CLP) in C57Bl/6 mice. We demonstrate that Nod1 and Nod2 are not involved in the release of chemokines and recruitment of neutrophils to the infectious site during CLP-induced septic peritonitis because these events were similar in wild-type, Nod1-, Nod2-, Nod1/Nod2- and Rip2-deficient mice. Consequently, the local and systemic bacterial loads were not altered. Accordingly, neither Nod1 nor Nod2 was involved in the production of the circulating cytokines and in the accumulation of leukocytes in the lungs. By contrast, we showed that MyD88-dependent signaling is crucial for the establishment of the local inflammatory response during CLP-induced sepsis. MyD88-deficient mice were susceptible to sepsis because of an impaired local production of chemokines and defective neutrophil recruitment to the infection site. Altogether, these data show that Nod1, Nod2 and Rip2 are not required for local chemokine production and neutrophil recruitment during CLP-induced sepsis, and they reinforce the importance of MyD88-dependent signaling for initiation of a protective host response.
authors.affiliation: Faculdade de Medicina de Ribeiraő Preto, Departamento de Farmacologia, Universidade de São Paulo, Ribeiraő Preto, São Paulo, Brasil.
authors.forename: Fabiane
authors.initials: F
authors.lastname: Sônego
authors.affiliation: Faculdade de Medicina de Ribeiraő Preto, Departamento de Farmacologia, Universidade de São Paulo, Ribeiraő Preto, São Paulo, Brasil.
authors.forename: Fernanda V S
authors.initials: FV
authors.lastname: Castanheira
authors.affiliation: Faculdade de Medicina de Ribeiraő Preto, Departamento de Farmacologia, Universidade de São Paulo, Ribeiraő Preto, São Paulo, Brasil.
authors.forename: Paula G
authors.initials: PG
authors.lastname: Czaikoski
authors.affiliation: Faculdade de Medicina de Ribeiraő Preto, Departamento de Farmacologia, Universidade de São Paulo, Ribeiraő Preto, São Paulo, Brasil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Kanashiro
authors.affiliation: Faculdade de Medicina de Ribeiraő Preto, Departamento de Farmacologia, Universidade de São Paulo, Ribeiraő Preto, São Paulo, Brasil.
authors.forename: Fabricio O
authors.initials: FO
authors.lastname: Souto
authors.affiliation: Faculdade de Medicina de Ribeiraő Preto, Departamento de Farmacologia, Universidade de São Paulo, Ribeiraő Preto, São Paulo, Brasil.
authors.forename: Rafael O
authors.initials: RO
authors.lastname: França
authors.affiliation: Faculdade de Medicina de Ribeiraő Preto, Departamento de Farmacologia, Universidade de São Paulo, Ribeiraő Preto, São Paulo, Brasil.
authors.forename: Daniele C
authors.initials: DC
authors.lastname: Nascimento
authors.affiliation: Faculdade de Medicina de Ribeiraő Preto, Departamento de Farmacologia, Universidade de São Paulo, Ribeiraő Preto, São Paulo, Brasil.
authors.forename: Andressa
authors.initials: A
authors.lastname: Freitas
authors.affiliation: Faculdade de Medicina de Ribeiraő Preto, Departamento de Farmacologia, Universidade de São Paulo, Ribeiraő Preto, São Paulo, Brasil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Spiller
authors.affiliation: Faculdade de Medicina de Ribeiraő Preto, Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Universidade de São Paulo, Ribeiraő Preto, São Paulo, Brasil.
authors.forename: Larissa D
authors.initials: LD
authors.lastname: Cunha
authors.affiliation: Faculdade de Medicina de Ribeiraő Preto, Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Universidade de São Paulo, Ribeiraő Preto, São Paulo, Brasil.
authors.forename: Dario S
authors.initials: DS
authors.lastname: Zamboni
authors.affiliation: Faculdade de Medicina de Ribeiraő Preto, Departamento de Farmacologia, Universidade de São Paulo, Ribeiraő Preto, São Paulo, Brasil.
authors.forename: José C
authors.initials: JC
authors.lastname: Alves-Filho
authors.affiliation: Faculdade de Medicina de Ribeiraő Preto, Departamento de Farmacologia, Universidade de São Paulo, Ribeiraő Preto, São Paulo, Brasil.
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D018805:Sepsis / Q000235:genetics / Q000378:metabolism*
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506255:Ripk2 protein, mouse
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