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Leptospiral outer membrane protein LipL32 induces inflammation and kidney injury in zebrafish larvae
Ming-Yang Chang1, Yi-Chuan Cheng2, Shen-Hsing Hsu1
1Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
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.
Insights
Leptospira outer membrane protein LipL32 causes kidney injury by increasing macrophage infiltration and disrupting kidney structure. Toll-like receptor 2 (TLR2) mediates this LipL32-induced renal pathology in zebrafish.
Area of Science:
- Nephrology
- Infectious Diseases
- Immunology
Background:
- Leptospirosis, a zoonotic disease, is a significant cause of acute kidney injury (AKI) and can lead to severe complications.
- The outer membrane protein LipL32 is conserved in pathogenic Leptospira species, but its role in kidney injury is not fully understood.
Purpose of the Study:
- To investigate the role of LipL32 in the pathogenesis of leptospirosis-induced renal injury using a zebrafish model.
- To elucidate the molecular mechanisms underlying LipL32-mediated kidney damage.
Main Methods:
- Zebrafish larvae were exposed to Leptospira or injected with LipL32 mRNA/protein.
- Kidney structure, macrophage infiltration, and NA-K-ATPase localization were assessed.
- The involvement of Toll-like receptors (TLRs) was examined using morpholino knockdown.
Main Results:
- Leptospira infection and LipL32 administration induced acute tubular injury in zebrafish pronephric ducts.
- LipL32 increased macrophage accumulation and disrupted NA-K-ATPase localization, impairing kidney structure.
- Knockdown of tlr2, but not tlr4, significantly reduced LipL32-induced leukocyte infiltration and kidney injury.
Conclusions:
- LipL32 contributes to renal pathology in leptospirosis, highlighting its potential virulence factor.
- The study validates zebrafish as a model for studying leptospiral infection mechanisms.
- TLR2 plays a critical role in mediating LipL32-induced kidney injury.
