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

Published online by Cambridge University Press:  18 December 2018

A. Rodrigues
Affiliation:
Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal
G. Alexandre-Pires
Affiliation:
CIISA, Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Av. Universidade Técnica, 1300-477 Lisbon, Portugal
A. Valério-Bolas
Affiliation:
Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal
D. Santos-Mateus
Affiliation:
Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal
M. Rafael-Fernandes
Affiliation:
Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal
M. A. Pereira
Affiliation:
Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal
D. Ligeiro
Affiliation:
IPST-Centro de Sangue e Transplantação de Lisboa, Alameda das Linhas de Torres 117, 1749-005 Lisbon, Portugal
T. Nunes
Affiliation:
Microscopy Center, Faculty of Sciences, Campo Grande, 1749-016 Lisboa, Portugal
R. Alves-Azevedo
Affiliation:
Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal
S. Lopes-Ventura
Affiliation:
Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal
M. Santos
Affiliation:
CIISA, Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Av. Universidade Técnica, 1300-477 Lisbon, Portugal
A. M. Tomás
Affiliation:
I3S, Instituto de Investigação e Inovação em Saúde, IBMC, Instituto de Biologia Molecular e Celular and, Instituto de Ciências Biomédicas Abel Salazar, ICBAS Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
I. Pereira da Fonseca
Affiliation:
CIISA, Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Av. Universidade Técnica, 1300-477 Lisbon, Portugal
G. Santos-Gomes
Affiliation:
Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal
Corresponding
E-mail address:

Abstract

Hepatocytes constitute the majority of hepatic cells, and play a key role in controlling systemic innate immunity, via pattern-recognition receptors (PRRs) and by synthesizing complement and acute phase proteins. Leishmania infantum, a protozoan parasite that causes human and canine leishmaniasis, infects liver by establishing inside the Kupffer cells. The current study proposes the elucidation of the immune response generated by dog hepatocytes when exposed to L. infantum. Additionally, the impact of adding leishmanicidal compound, meglumine antimoniate (MgA), to parasite-exposed hepatocytes was also addressed. L. infantum presents a high tropism to hepatocytes, establishing strong membrane interactions. The possibility of L. infantum internalization by hepatocytes was raised, but not confirmed. Hepatocytes were able to recognize parasite presence, inducing PRRs [nucleotide oligomerization domain (NOD)1, NOD2 and Toll-like receptor (TLR)2] gene expression and generating a mix pro- and anti-inflammatory cytokine response. Reduction of cytochrome P 450s enzyme activity was also observed concomitant with the inflammatory response. Addition of MgA increased NOD2, TLR4 and interleukin 10 gene expression, indicating an immunomodulatory role for MgA. Hepatocytes seem to have a major role in coordinating liver's innate immune response against L. infantum infection, activating inflammatory mechanisms, but always balancing the inflammatory response in order to avoid cell damage.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2018 

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