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1530414 
Journal Article 
TLR2, TLR4 and the MYD88 Signaling Pathway Are Crucial for Neutrophil Migration in Acute Kidney Injury Induced by Sepsis 
Castoldi, A; Braga, TT; Correa-Costa, M; Aguiar, CF; Bassi, EJ; Correa-Silva, R; Elias, RM; Salvador, F; Moraes-Vieira, PM; Cenedeze, MA; Reis, MA; Hiyane, MI; Pacheco-Silva, A; Goncalves, GM; Saraiva Camara, NO 
2012 
1 
PLoS ONE
EISSN: 1932-6203 
7 
5 
22655058 
WOS:000305338900034 
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.