Leptospiral outer membrane protein LipL32 induces inflammation and kidney injury in zebrafish larvae.
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.
Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Ming-Yang
MY
Chang
Department of Biochemistry and Molecular Biology, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Yi-Chuan
YC
Cheng
Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Shen-Hsing
SH
Hsu
Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Tsu-Lin
TL
Ma
Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Li-Fang
LF
Chou
Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Hsiang-Hao
HH
Hsu
Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Ya-Chung
YC
Tian
Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Yung-Chang
YC
Chen
Department of Life Science and Institute of Bioinformatics and Structural Biology, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan.
Yuh-Ju
YJ
Sun
Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Cheng-Chieh
CC
Hung
Department of Life Science and Institute of Bioinformatics and Structural Biology, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan.
Rong-Long
RL
Pan
Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Chih-Wei
CW
Yang
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000196:embryology / Q000235:genetics / Q000382:microbiology; D007668:Kidney / Q000196:embryology / Q000382:microbiology; D007674:Kidney Diseases / Q000196:embryology / Q000235:genetics / Q000382:microbiology; D007919:Leptospira / Q000235:genetics / Q000378:metabolism*; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D060910:Pronephros / Q000196:embryology / Q000382:microbiology; D015027:Zebrafish / Q000196:embryology / Q000382:microbiology
D001425:Bacterial Outer Membrane Proteins; C406589:LipL32 protein, Leptospira; D008074:Lipoproteins