TLR2, TLR4 and the MYD88 signaling pathway are crucial for neutrophil migration in acute kidney injury induced by sepsis

• Published in: PloS one Vol. 7; no. 5; p. e37584
• Main Authors: Castoldi, Angela, Braga, Tárcio Teodoro, Correa-Costa, Matheus, Aguiar, Cristhiane Fávero, Bassi, Ênio José, Correa-Silva, Reinaldo, Elias, Rosa Maria, Salvador, Fábia, Moraes-Vieira, Pedro Manoel, Cenedeze, Marcos Antônio, Reis, Marlene Antônia, Hiyane, Meire Ioshie, Pacheco-Silva, Álvaro, Gonçalves, Giselle Martins, Saraiva Câmara, Niels Olsen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24-05-2012; Public Library of Science (PLoS)
• Subjects: Acute Kidney Injury - etiology; Acute Kidney Injury - genetics; Acute Kidney Injury - immunology; Acute Kidney Injury - pathology; Adapter proteins; Animals; Apoptosis; Biology; Cecum; Chemokines; Corynebacterium; Cytokines; Cytokines - immunology; Epidermal growth factor; Gene Deletion; House mouse; Hypoxia; Immunity; Infection; Infiltration; Inflammation; Innate immunity; Kidney - immunology; Kidney - metabolism; Kidney - pathology; Kidneys; Leukocyte migration; Leukocytes (neutrophilic); Male; Medicine; Mice; Mice, Inbred C57BL; Mice, Knockout; Multiple organ dysfunction syndrome; MyD88 protein; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - immunology; Neutrophil Infiltration; Neutrophils; Neutrophils - immunology; Neutrophils - metabolism; Neutrophils - pathology; Peritoneum; Permeability; Renal function; Rodents; Sepsis; Sepsis - complications; Signal Transduction; Signaling; TLR2 protein; TLR4 protein; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - immunology; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - immunology; Toll-like receptors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0037584

The aim of this study was to investigate the role of TLR2, TLR4 and MyD88 in sepsis-induced AKI. C57BL/6 TLR2(-/-), TLR4(-/-) and MyD88(-/-) male mice were subjected to sepsis by cecal ligation and puncture (CLP). Twenty four hours later, kidney tissue and blood samples were collected for analysis. The TLR2(-/-), TLR4(-/-) and MyD88(-/-) mice that were subjected to CLP had preserved renal morphology, and fewer areas of hypoxia and apoptosis compared with the wild-type C57BL/6 mice (WT). MyD88(-/-) mice were completely protected compared with the WT mice. We also observed reduced expression of proinflammatory cytokines in the kidneys of the knockout mice compared with those of the WT mice and subsequent inhibition of increased vascular permeability in the kidneys of the knockout mice. The WT mice had increased GR1(+low) cells migration compared with the knockout mice and decreased in GR1(+high) cells migration into the peritoneal cavity. The TLR2(-/-), TLR4(-/-), and MyD88(-/-) mice had lower neutrophil infiltration in the kidneys. Depletion of neutrophils in the WT mice led to protection of renal function and less inflammation in the kidneys of these mice. Innate immunity participates in polymicrobial sepsis-induced AKI, mainly through the MyD88 pathway, by leading to an increased migration of neutrophils to the kidney, increased production of proinflammatory cytokines, vascular permeability, hypoxia and apoptosis of tubular cells.