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The current study proposes the elucidation of the immune response generated by dog hepatocytes when exposed to<jats:italic>L. infantum<\/jats:italic>. Additionally, the impact of adding leishmanicidal compound, meglumine antimoniate (MgA), to parasite-exposed hepatocytes was also addressed.<jats:italic>L. infantum<\/jats:italic>presents a high tropism to hepatocytes, establishing strong membrane interactions. The possibility of<jats:italic>L. infantum<\/jats:italic>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<jats:italic>L. infantum<\/jats:italic>infection, activating inflammatory mechanisms, but always balancing the inflammatory response in order to avoid cell damage.<\/jats:p>","DOI":"10.1017\/s0031182018002068","type":"journal-article","created":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T13:32:35Z","timestamp":1545139955000},"page":"753-764","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":8,"title":["Dog hepatocytes are key effector cells in the liver innate immune response to<i>Leishmania infantum<\/i>"],"prefix":"10.1017","volume":"146","author":[{"given":"A.","family":"Rodrigues","sequence":"first","affiliation":[]},{"given":"G.","family":"Alexandre-Pires","sequence":"additional","affiliation":[]},{"given":"A.","family":"Val\u00e9rio-Bolas","sequence":"additional","affiliation":[]},{"given":"D.","family":"Santos-Mateus","sequence":"additional","affiliation":[]},{"given":"M.","family":"Rafael-Fernandes","sequence":"additional","affiliation":[]},{"given":"M. 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