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Immunodetection of hepatic stellate cells in dogs with visceral leishmaniasis

Parasitology Research volume 117, pages 1829–1837 (2018)Cite this article

Abstract

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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Acknowledgements

The authors wish to acknowledge the Zoonosis Control Center of Araçatuba for providing the animals of this study.

Funding

Financial assistance was provided by FAPESP, Pamela Rodrigues Reina Moreira (Fundação de Amparo à Pesquisa do Estado de São Paulo; Procedural number 2013/00763-4). Paulo Henrique Leal Bertolo (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior). Natália Cassaro Marques (Conselho Nacional de Pesquisa e desenvolvimento, PIBIC-CNPq).

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Affiliations

  1. Departamento de Patologia Veterinária, Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista (UNESP) , Via de Acesso Prof. Paulo Donato Castellane, s / n , Jaboticabal , SP , 14884-900 , Brasil

    Natália Cassaro Marques , Pamela Rodrigues Reina Mo reira , Paulo Henrique Leal Bertolo  & Rosemeri de Oliveira Vasconcelos

  2. Universidade do Mississipi Medical Center , Jackson , MS, USA

    Fábio Nelson Gava

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  1. Natália Cassaro Marques
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  2. Pamela Rodrigues Reina Mo reira
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  3. Paulo Henrique Leal Bertolo
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  4. Fábio Nelson Gava
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  5. Rosemeri de Oliveira Vasconcelos
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Corresponding author

Correspondence to Pamela Rodrigues Reina Mo reira .

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Ethical approval

The design for this study was approved by the Ethics and Animal Welfare Committee (CEBEA no. 11976/15) of FCAV/UNESP, Jaboticabal, state of São Paulo, Brazil.

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The authors declare that they have no conflict of interest.

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Marques , N.C., Mo reira , P.R.R., Bertolo , P.H.L. et al. Immunodetection of hepatic stellate cells in dogs with visceral leishmaniasis. Parasitol Res 117, 1829–1837 (2018). https://doi.org/10.1007/s00436-018-5870-2

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  • DOI: https://doi.org/10.1007/s00436-018-5870-2

Keywords

  • Ito cells
  • Liver
  • Leishmania infantum
  • TGF-β
  • Hepatic fibrosis