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Leptospiral outer membrane protein LipL32 induces inflammation and kidney injury in zebrafish larvae.

ABSTRACT: Leptospirosis is an often overlooked cause of acute kidney injury that can lead to multiple organ failure and even death. The principle protein that conserved in many pathogenic leptospires is the outer membrane protein LipL32. However, the role of LipL32 in the pathogenesis of renal injury in leptospirosis is not entirely clear. Here we studied the effects of LipL32 on the developing kidney in zebrafish larvae. Incubation of zebrafish larvae with Leptospira santarosai serovar Shermani induced acute tubular injury predominantly in the proximal pronephric ducts. Furthermore, microinjection of lipl32 mRNA or recombinant LipL32 protein into zebrafish larvae increased macrophage accumulation and disrupted the basolateral location of NA-K-ATPase in pronephric ducts. These changes led to substantial impairment of the pronephric kidney structure. We further demonstrated that morpholino knockdown of tlr2, but not tlr4, reduced the LipL32-induced leukocyte infiltration and kidney injury. These data demonstrate that LipL32 contributes to the renal pathology in leptospirosis and gives some clues to the potential virulence of LipL32. Our results support the use of zebrafish as a model organism for studying the disease mechanism of leptospiral infection. This model might permit the future exploration of the virulence and molecular pathways of different leptospiral outer membrane proteins.

SUBMITTER: Chang MY

PROVIDER: S-EPMC4899798 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Leptospiral outer membrane protein LipL32 induces inflammation and kidney injury in zebrafish larvae.

Chang Ming-Yang MY Cheng Yi-Chuan YC Hsu Shen-Hsing SH Ma Tsu-Lin TL Chou Li-Fang LF Hsu Hsiang-Hao HH Tian Ya-Chung YC Chen Yung-Chang YC Sun Yuh-Ju YJ Hung Cheng-Chieh CC Pan Rong-Long RL Yang Chih-Wei CW

Scientific reports 20160609

Leptospirosis is an often overlooked cause of acute kidney injury that can lead to multiple organ failure and even death. The principle protein that conserved in many pathogenic leptospires is the outer membrane protein LipL32. However, the role of LipL32 in the pathogenesis of renal injury in leptospirosis is not entirely clear. Here we studied the effects of LipL32 on the developing kidney in zebrafish larvae. Incubation of zebrafish larvae with Leptospira santarosai serovar Shermani induced a ...[more]

PMID: 27278903

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Project description:Chronic ethanol ingestion mildly damages liver through oxidative stress and lipid oxidation, which is ameliorated by dietary supplementation with the anti-inflammatory β-amino acid taurine. Kidney, like liver, expresses cytochrome P450 2E1 that catabolizes ethanol with free radical formation, and so also may be damaged by ethanol catabolism. Sudden loss of kidney function, and not liver disease itself, foreshadows mortality in patients with alcoholic hepatitis [J. Altamirano, Clin. Gastroenterol. Hepatol. 2012, 10:65]. We found that ethanol ingestion in the Lieber-deCarli rat model increased kidney lipid oxidation, 4-hydroxynonenal protein adduction, and oxidatively truncated phospholipids that attract and activate leukocytes. Chronic ethanol ingestion increased myeloperoxidase-expressing cells in kidney and induced an inflammatory cell infiltrate. Apoptotic terminal deoxynucleotidyl transferase nick-end labeling-positive cells and active caspase-3 increased in kidney after ethanol ingestion, with reduced filtration with increased circulating blood urea nitrogen (BUN) and creatinine. These events were accompanied by release of albumin, myeloperoxidase, and the acute kidney injury biomarkers kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin, and cystatin c into urine. Taurine sequesters HOCl from myeloperoxidase of activated leukocytes, and taurine supplementation reduced renal lipid oxidation, reduced leukocyte infiltration, and reduced the increase in myeloperoxidase-positive cells during ethanol feeding. Taurine supplementation also normalized circulating BUN and creatinine levels and suppressed enhanced myeloperoxidase, albumin, KIM-1, and cystatin c in urine. Thus, chronic ethanol ingestion oxidatively damages kidney lipids and proteins, damages renal function, and induces acute kidney injury through an inflammatory cell infiltrate. The anti-inflammatory nutraceutical taurine effectively interrupts this ethanol-induced inflammatory cycle in kidney.

Dataset Information

Leptospiral outer membrane protein LipL32 induces inflammation and kidney injury in zebrafish larvae.

Publications

Leptospiral outer membrane protein LipL32 induces inflammation and kidney injury in zebrafish larvae.

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