Influence of apoptosis on liver and spleen resistance in dogs with visceral leishmaniosis

Moreira, Pâmela Rodrigues Reina; Franciscato, Douglas Augusto; Rossit, Sabrina Micelli; Munari, Danísio Prado; Vasconcelos, Rosemeri de Oliveira

doi:10.1590/s1984-29612016054

Cited by 9 publications

(15 citation statements)

References 19 publications

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“…the immunohistochemical characterization of these cells should be encouraged to increase the accuracy of the results and to better understand the potential changes in splenic function. In the present study, splenic granulomas were significantly associated with the presence of parasites in this tissue, as previously described in splenic infection in cases of CVL (MoReIRa et al, 2016;SaNt'aNa et al, 2008;taSCa et al, 2009), and have also been associated with disorganization of the splenic architecture (MoReIRa et al, 2016;taSCa et al, 2009), particularly in advanced cases of the disease (MoReIRa et al, 2016).…”

Section: Discussionsupporting

confidence: 87%

“…As for livers, mild mononuclear infiltrate with predominantly portal location was observed, which is in accordance with the findings by toRReS et al (2016). Infiltrate composition with lymphocytes, plasma cells, and macrophages was described by previous studies (MeLo et al, 2009;MoReIRa et al, 2016), along with the presence of vacuolar changes, which were recently reported by MoReIRa et al (2016). In the present study, since the non granulomatous inflammation in the liver was not accompanied by hepatocellular necrosis or fibrosis, it is reasonable to assume that it is consistent with a nonspecific reactive response to an extra-hepatic injury ( VaN deN INGH et al, 2006).…”

Section: Discussionsupporting

confidence: 84%

“…In the present study, since the non granulomatous inflammation in the liver was not accompanied by hepatocellular necrosis or fibrosis, it is reasonable to assume that it is consistent with a nonspecific reactive response to an extra-hepatic injury ( VaN deN INGH et al, 2006). In contrast, the hepatic granulomas are findings of great relevance in CVL, having been widely described (MeLo et al, 2009;MoReIRa et al, 2016; 2007). Granulomatous hepatitis in dogs may be a response to either hepatic or extra-hepatic processes.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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Visceral leishmaniasis (VL) is a zoonotic disease with a canine urban reservoir in South America. Dogs from an endemic area within Brazil, which were naturally infected with Leishmania infantum, and those presenting severe clinical (SC), mild, or no clinical (MNC) disease, were evaluated. Parasite load, histopathology, and cytokine and iNOS mRNA expressions were assessed in the spleen and liver in order to determine the potential markers for disease susceptibility or resistance. As a result, dogs with both SC and MNC had high parasite loads; IFN-γ was the most expressive cytokine in both organs, along with IL-6 and IL-4 being detected in the spleen and liver, and IL-10 only in liver. The hepatic tissue presented higher medians for IFN-γ and IL-10, and was the main organ to produce cytokines with hepatic IL-10 suggesting a regulatory follow up. Granulomas were detected in both organs; however, when absent in spleen, they were associated with elevated IL-6 levels, thus highlighting the anti-inflammatory role of IL-6. Microscopic lesions in the spleen were predominantly characterized by an extensively disorganized white pulp and splenic response was suggested as sub optimized. Parasite load, tissue damage, and immunological response may vary in the dogs with similar clinical symptoms, which may not be a good parameter for assessing the animal's susceptibility to VL. RESUMO:A Leishmaniose visceral (LV) é uma doença zoonótica com reservatório canino na América do Sul. Cães oriundos de área endemica brasileira, naturalmente infectados por Leishmania infantum, apresentando doença clínica severa (CS) ou doença branda ou ausente (BA) foram avaliados. Carga parasitária, histopatologia e expressão de mRNA de citocinas e iNOS foram analisados em baço e fígado, buscando determinar possíveis marcadores de susceptibilidade ou resistência à doença. Como principais resultados, tanto cães CS como BA apresentaram alta carga parsitária. IFN-γ foi a citocina mais expressiva em ambos os órgãos, sendo IL-6 e IL-4 também detectadas em baço e fígado e IL-10 em fígado. No tecido hepático foram encontradas as maiores medianas de IFN-γ e IL-10, sendo o fígado o principal órgão produtor de citocinas, com IL-10 sugerindo acompanhamento regulatório. Granulomas foram detectados em ambos os órgãos. Quando de sua ausência no baço, essa foi associada à elevação dos níveis de IL-6, salientando o papel anti-inflamatório dessa citocina. Alterações microscópicas foram principalmente caracterizadas por extensiva desorganização de polpa branca, com a resposta esplência sendo sugerida como subotimizada. Carga parasitária, dano tecidual e resposta immune variaram mesmo em cães com quadros clínicos similares, não sendo, portanto, a análise clínica um bom parâmetro para avaliação de susceptibilidade animal à LV. Palavras-chave: Leishmaniose visceral, imunopatologia, infecção canina, histopatologia, citocinas caninas. PaRaSItoLoGY

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…The large number of cells (lymphocytes) undergoing apoptosis in the spleen of dogs with visceral leishmaniosis was correlated with the parasite load, which suggested that this process could be a contributing factor for the survival of the protozoon in this organ [13]. Of note, splenectomy was considered one of the main clinical outbreaks of hemotropic Mycoplasma spp.…”

Section: Introductionmentioning

confidence: 99%

Molecular detection of vector-borne pathogens in blood and splenic samples from dogs with splenic disease

et al. 2017

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BackgroundThe spleen is a highly perfused organ involved in the immunological control and elimination of vector-borne pathogens (VBP), which could have a fundamental role in the pathogenesis of splenic disease. This study aimed to evaluate certain VBP in samples from dogs with splenic lesions.MethodsSeventy-seven EDTA-blood and 64 splenic tissue samples were collected from 78 dogs with splenic disease in a Mediterranean area. Babesia spp., Bartonella spp., Ehrlichia/Anaplasma spp., Hepatozoon canis, Leishmania infantum, hemotropic Mycoplasma spp. and Rickettsia spp. were targeted using PCR assays. Sixty EDTA-blood samples from dogs without evidence of splenic lesions were included as a control group.ResultsMore than half (51.56%) of the biopsies (33/64) were consistent with benign lesions and 48.43% (31/64) with malignancy, mostly hemangiosarcoma (25/31). PCR yielded positive results in 13 dogs with spleen alterations (16.67%), for Babesia canis (n = 3), Babesia gibsoni (n = 2), hemotropic Mycoplasma spp. (n = 2), Rickettsia massiliae (n = 1) and “Babesia vulpes” (n = 1), in blood; and for B. canis, B. gibsoni, Ehrlichia canis and L. infantum (n = 1 each), in spleen. Two control dogs (3.3%) were positive for B. gibsoni and H. canis (n = 1 each). Benign lesions were detected in the 61.54% of infected dogs (8/13); the remaining 38.46% were diagnosed with malignancies (5/13). Infection was significantly associated to the presence of splenic disease (P = 0.013). There was no difference in the prevalence of infection between dogs with benign and malignant splenic lesions (P = 0.69); however B. canis was more prevalent in dogs with hemangiosarcoma (P = 0.006).ConclusionsVBP infection could be involved in the pathogenesis of splenic disease. The immunological role of the spleen could predispose to alterations of this organ in infected dogs. Interestingly, all dogs with B. canis infection were diagnosed with hemangiosarcoma in the present survey. As previously reported, results support that VBP diagnosis could be improved by analysis of samples from different tissues. The sample size included here warrants further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-017-2074-z) contains supplementary material, which is available to authorized users.

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Immunodetection of hepatic stellate cells in dogs with visceral leishmaniasis

et al. 2018

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Hepatic stellate cells (HSC), or Ito cells, store vitamin A when at rest but undergo phenotypic changes in situations of liver injury, which may induce fibrosis, and they may participate in the immune response in the liver. The objective of the present study was to investigate the role of HSC in the livers of dogs with visceral leishmaniasis (VL). Twenty-eight livers from dogs infected with VL that were living in an area endemic for the disease were evaluated, among which 13 were asymptomatic (A) and 15 were symptomatic (S). A control group (C) was formed by five dogs from an area that was not endemic for VL. These organs were subjected to histopathological analysis (Masson's trichrome for fibrosis) and immunohistochemical analysis (Leishmania, smooth-muscle α-actin and TGF-β). In the livers from the symptomatic dogs, a moderate to severe granulomatous inflammatory reaction was observed in the capsule and in the portal, centrilobular and intralobular regions. In the asymptomatic dogs, there was slight to moderate presence of granulomas, and these were even absent in some dogs. The intensity of hepatic fibrosis was predominantly low in the infected dogs (A and S), and fibrosis was absent in the control group. The immunomarking of HSC in the infected groups (A and S) differed significantly (P = 0.0153) from that of the control group. The symptomatic dogs presented the largest number of positive cells. This group also presented a larger number of parasitized macrophages, but did not differ statistically from the asymptomatic group (P > 0.05). The cytokine TGF-β was only detected at low levels, and only in the infected animals, but this did not differ from the control group. Immunomarking for HSC was observed mainly in the nuclei of cells present in the hepatic granulomas of symptomatic dogs and in the sinusoids of the asymptomatic dogs. It was concluded that in the livers of dogs with VL, the HSC are activated and participate in the hepatic response to the parasite. The cytokine TGF-β may be involved in this activation, but in the chronic phase of the infection, this cytokine was detected at lower proportions. It is possible that HSC may also contribute towards chemotaxis of leukocytes for the hepatic compartment, along with other cell types such as Kupffer cells.

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Influence of apoptosis on liver and spleen resistance in dogs with visceral leishmaniosis

Cited by 9 publications

References 19 publications

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

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

Molecular detection of vector-borne pathogens in blood and splenic samples from dogs with splenic disease

Immunodetection of hepatic stellate cells in dogs with visceral leishmaniasis

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