Activation of Autophagy and Nucleotide-Binding Domain Leucine-Rich Repeat–Containing-Like Receptor Family, Pyrin Domain–Containing 3 Inflammasome during Leishmania infantum–Associated Glomerulonephritis

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