TLR2, TLR4 and the MYD88 signaling pathway are crucial for neutrophil migration in acute kidney injury induced by sepsis.
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.
Disciplina de Nefrologia, Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Angela
A
Castoldi
Tárcio Teodoro
TT
Braga
Matheus
M
Correa-Costa
Cristhiane Fávero
CF
Aguiar
Ênio José
ÊJ
Bassi
Reinaldo
R
Correa-Silva
Rosa Maria
RM
Elias
Fábia
F
Salvador
Pedro Manoel
PM
Moraes-Vieira
Marcos Antônio
MA
Cenedeze
Marlene Antônia
MA
Reis
Meire Ioshie
MI
Hiyane
Álvaro
Á
Pacheco-Silva
Giselle Martins
GM
Gonçalves
Niels Olsen
NO
Saraiva Câmara
D058186:Acute Kidney Injury / Q000209:etiology* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000818:Animals; D016207:Cytokines / Q000276:immunology; D017353:Gene Deletion; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology*; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018805:Sepsis / Q000150:complications*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4