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

Autor:	Esch KJ; Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa., Schaut RG; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa., Lamb IM; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa., Clay G; Inflammation Program, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa., Morais Lima ÁL; Department of Biochemistry, Institute of Tropical Medicine, Federal University of Rio Grande do Norte, Natal, Brazil., do Nascimento PR; Department of Biochemistry, Institute of Tropical Medicine, Federal University of Rio Grande do Norte, Natal, Brazil., Whitley EM; Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa., Jeronimo SM; Department of Biochemistry, Institute of Tropical Medicine, Federal University of Rio Grande do Norte, Natal, Brazil., Sutterwala FS; Inflammation Program, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa., Haynes JS; Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa., Petersen CA; 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.
Jazyk:	angličtina
Zdroj:	The American journal of pathology [Am J Pathol] 2015 Aug; Vol. 185 (8), pp. 2105-17. Date of Electronic Publication: 2015 Jun 13.
DOI:	10.1016/j.ajpath.2015.04.017
Abstrakt:	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. (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu