Activation of autophagy and nucleotide-binding domain leucine-rich repeat-containing-like receptor family, pyrin domain-containing 3 inflammasome during Leishmania infantum-associated glomerulonephritis

Kevin J Esch; Robert G Schaut; Ian M Lamb; Gwendolyn Clay; Ádila L Morais Lima; Paulo R P do Nascimento; Elizabeth M Whitley; Selma M B Jeronimo; Fayyaz S Sutterwala; Joseph S Haynes; Christine A Petersen

doi:10.1016/j.ajpath.2015.04.017

Back

Activation of autophagy and nucleotide-binding domain leucine-rich repeat-containing-like receptor family, pyrin domain-containing 3 inflammasome during Leishmania infantum-associated glomerulonephritis

Journal article

Open access

Peer reviewed

Activation of autophagy and nucleotide-binding domain leucine-rich repeat-containing-like receptor family, pyrin domain-containing 3 inflammasome during Leishmania infantum-associated glomerulonephritis

Kevin J Esch, Robert G Schaut, Ian M Lamb, Gwendolyn Clay, Ádila L Morais Lima, Paulo R P do Nascimento, Elizabeth M Whitley, Selma M B Jeronimo, Fayyaz S Sutterwala, Joseph S Haynes, …

The American journal of pathology, Vol.185(8), pp.2105-2117

08/2015

DOI: 10.1016/j.ajpath.2015.04.017

PMCID: PMC4530124

PMID: 26079813

Files and links (1)

url

https://doi.org/10.1016/j.ajpath.2015.04.017View

Published (Version of record) Open Access

Abstract

Chronic kidney disease is a major contributor to human and companion animal morbidity and mortality. Renal complications are sequelae of canine and human visceral leishmaniasis (VL). Despite the high incidence of infection-mediated glomerulonephritis, little is known about pathogenesis of VL-associated renal disease. Leishmania infantum-infected dogs are a naturally occurring model of VL-associated glomerulonephritis. Membranoproliferative glomerulonephritis type I [24 of 25 (96%)], with interstitial lymphoplasmacytic nephritis [23 of 25 (92%)], and glomerular and interstitial fibrosis [12 of 25 (48%)] were predominant lesions. An ultrastructural evaluation of glomeruli from animals with VL identified mesangial cell proliferation and interposition. Immunohistochemistry demonstrated significant Leishmania antigen, IgG, and C3b deposition in VL dog glomeruli. Asymptomatic and symptomatic dogs had increased glomerular nucleotide-binding domain leucine-rich repeat-containing-like receptor family, pyrin domain containing 3 and autophagosome-associated microtubule-associated protein 1 light chain 3 associated with glomerular lesion severity. Transcriptional analyses from symptomatic dogs confirmed induction of autophagy and inflammasome genes within glomeruli and tubules. On the basis of temporal VL staging, glomerulonephritis was initiated by IgG and complement deposition. This deposition preceded presence of nucleotide-binding domain leucine-rich repeat-containing-like receptor family, pyrin domain containing 3-associated inflammasomes and increased light chain 3 puncta indicative of autophagosomes in glomeruli from dogs with clinical VL and renal failure. These findings indicate potential roles for inflammasome complexes in glomerular damage during VL and autophagy in ensuing cellular responses.

Leishmania infantum

Inflammasomes - metabolism

Kidney Glomerulus - parasitology

Autophagy - physiology

Kidney Glomerulus - pathology

Glomerulonephritis - metabolism

Leishmaniasis, Visceral - metabolism

Leishmaniasis, Visceral - veterinary

Animals

Carrier Proteins - metabolism

Dogs

Kidney Glomerulus - metabolism

Leishmaniasis, Visceral - complications

Glomerulonephritis - parasitology

Glomerulonephritis - veterinary

Details

Title: Subtitle: Activation of autophagy and nucleotide-binding domain leucine-rich repeat-containing-like receptor family, pyrin domain-containing 3 inflammasome during Leishmania infantum-associated glomerulonephritis
Creators: Kevin J Esch - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa
Robert G Schaut - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa
Ian M Lamb - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa
Gwendolyn Clay - Inflammation Program, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa
Ádila L Morais Lima - Department of Biochemistry, Institute of Tropical Medicine, Federal University of Rio Grande do Norte, Natal, Brazil
Paulo R P do Nascimento - Department of Biochemistry, Institute of Tropical Medicine, Federal University of Rio Grande do Norte, Natal, Brazil
Elizabeth M Whitley - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa
Selma M B Jeronimo - Department of Biochemistry, Institute of Tropical Medicine, Federal University of Rio Grande do Norte, Natal, Brazil
Fayyaz S Sutterwala - Inflammation Program, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa
Joseph S Haynes - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa
Christine A Petersen - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa. Electronic address: christine-petersen@uiowa.edu
Resource Type: Journal article
Publication Details: The American journal of pathology, Vol.185(8), pp.2105-2117
DOI: 10.1016/j.ajpath.2015.04.017
PMID: 26079813
PMCID: PMC4530124
NLM abbreviation: Am J Pathol
ISSN: 1525-2191
eISSN: 1525-2191
Publisher: United States
Grant note: R21 AI088051 / NIAID NIH HHS P30 ES005605 / NIEHS NIH HHS AI088051 / NIAID NIH HHS T32 GM007337 / NIGMS NIH HHS P50 AI030639 / NIAID NIH HHS R01 AI087630 / NIAID NIH HHS
Language: English
Date published: 08/2015
Academic Unit: Epidemiology; Internal Medicine
Record Identifier: 9983996079402771

Metrics

23 Record Views

35 Times Cited - Web of Science

See more details