Hepatic granulomas in canine visceral leishmaniasis and clinical status

Abstract

The histopathological description of intralobular hepatic granulomas in animals with a defined clinical status (asymptomatic, oligosymptomatic and symptomatic animals) was reported. Seventy-one mongrel dogs naturally infected with Leishmania chagasi were obtained from two Brazilian endemic areas: João Pessoa, PB and Belo Horizonte, MG. The hepatic parasite load was determined and compared to granuloma formation. Liver fragments from all infected animals showed remarkable leishmaniotic granulomatous inflammatory reaction. Granulomas with variable size were constituted by macrophages (parasitized or not with amastigotes of L. chagasi), some epithelioid cells, small numbers of lymphocytes, plasma cells, and rare neutrophils. Asymptomatic dogs had higher numbers of granulomas than oligosymptomatic and symptomatic animals from both geographical regions. However, the average diametric size of granulomas was very heterogeneous in all groups, independently of the geographic region (P>0.05). Parasite tissue load did not show any difference among liver fragments of all animals, especially when considering the defined clinical status and/or their geographic origin.

Parasite load, iNOS and cytokine profiles, and histopathological aspects of Leishmania infantum infection in dogs with different clinical presentations

“…In the course of leishmaniasis, granulomas are associated with the resolution and clearance of the liver infection in the murine model (LoeuILLet et al, 2016) and allow local concentration of inflammatory cytokines that activate the leishmanicidal mechanisms of Kupffer cells (SRIVaStaVa et al, 2016), which may explain the higher IFN-γ median found in samples with granuloma. although, there are other causes for hemosiderin presence, this finding in the liver was previously reported in CVL (SaNt'aNa et al, 2007), and possibly the low nitric oxide production in symptomatic animals is associated with higher rates of iron deposition on tissue (SouZa et al, 2014), which corroborates our results. Moreover, evidence suggested that symptomatic dogs present increased lipid peroxidation and tissue iron deposition associated with enhanced levels of antioxidant enzymes; and therefore, these changes in the oxidative balance may aggravate the pathological process in CVL (SouZa et al, 2014).…”

“…In this sense, BoRJa et al (2016) also reported no significant association between the clinical manifestations and parasite load in the spleen of dogs naturally infected with L. infantum. Regarding hepatic analyses, Sant'ana et al (2007) also did not find any significant differences between the parasite load in liver and canine clinical status, similarly to the results obtained for the liver samples in this study. These findings are still in accordance with our recent previous results on lymph node parasite load and clinical evaluation in dogs, which presented no significant difference (de VaSCoNCeLoS et al, 2016).…”

“…all the obligatory cellular and humoral components enrolled in the immune response against the parasite are present in the spleen in large amounts (SRIVaStaVa et al, 2016). In the liver, several cells such as Kupffer (LoeuILLet et al, 2016;MeLo et al, 2009;MoReIRa et al, 2016;RodRIGueS et al, 2016;SaNt'aNa et al, 2007), t lymphocyte, and dendritic cells present interesting interactions (LoeuILLet et al, 2016;RodRIGueS et al, 2016).…”

Dog hepatocytes are key effector cells in the liver innate immune response toLeishmania infantum

“…Resolution of disease in this organ is associated with granuloma formation, which is one of the key features of hepatic resistance. The resolution of the infection in the liver (in humans, dogs and mouse models) is attributed to the development of a Th1-dominated granulomatous response, that is able to restrain the parasite dissemination and is characterized by high IFN-γ, IL-12 and TNF-α production through CD4 + T cells (Sant'Ana et al ., 2007; Melo et al ., 2009; Kaye and Beattie, 2016). IL-12 has been described, as an essential cytokine in the development of protective immunity against Leishmania.…”

“…Livers of asymptomatic dogs showed an effective immunity with well-organized granulomas able to isolate and restrain parasite spreading, in an immune environment of activated effector T cells, dendritic cells (DCs) and central memory cells. In contrast, liver of symptomatic dogs showed a non-organized and ineffective infiltrate of T cells and heavily parasitized KCs (Sant'Ana et al ., 2007; Murray, 2008). Despite these local responses, Leishmania is able to disseminate and produce symptomatic VL.…”