AUTHOR=Nadaes Natalia Rocha , Silva da Costa Leandro , Santana Raissa Couto , LaRocque-de-Freitas Isabel Ferreira , Vivarini Áislan de Carvalho , Soares Deivid Costa , Wardini Amanda Brito , Gazos Lopes Ulisses , Saraiva Elvira M. , Freire-de-Lima Celio Geraldo , Decote-Ricardo Debora , Pinto-da-Silva Lucia Helena 

TITLE=DH82 Canine and RAW264.7 Murine Macrophage Cell Lines Display Distinct Activation Profiles Upon Interaction With Leishmania infantum and Leishmania amazonensis

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.00247

DOI=10.3389/fcimb.2020.00247

ISSN=2235-2988

ABSTRACT=<p>Leishmaniasis is an anthropozoonotic disease, and dogs are considered the main urban reservoir of the parasite. Macrophages, the target cells of <italic>Leishmania sp</italic>., play an important role during infection. Although dogs have a major importance in the epidemiology of the disease, the majority of the current knowledge about <italic>Leishmania</italic>–macrophage interaction comes from murine experimental models. To assess whether the canine macrophage strain DH82 is an accurate model for the study of <italic>Leishmania</italic> interaction, we compared its infection by two species of <italic>Leishmania</italic> (<italic>Leishmania infantum</italic> and <italic>L. amazonensis</italic>) with the murine macrophage cell line (RAW264.7). Our results demonstrated that <italic>L. amazonensis</italic> survival was around 40% at 24 h of infection inside both macrophage cell lines; however, a reduction of 4.3 times in <italic>L. amazonensis</italic> infection at 48 h post-infection in RAW 264.7 macrophages was observed. The survival index of <italic>L. infantum</italic> in DH82 canine macrophages was around 3 times higher than that in RAW264.7 murine cells at 24 and 48 h post-infection; however, at 48 h a reduction in both macrophages was observed. Surprisingly at 24 h post-infection, NO and ROS production by DH82 canine cells stimulated with LPS or menadione or during <italic>Leishmania</italic> infection was minor compared to murine RAW264.7. However, basal arginase activity was higher in DH82 cells when compared to murine RAW264.7 cells. Analysis of the cytokines showed that these macrophages present a different response profile. <italic>L. infantum</italic> induced IL-12, and <italic>L. amazonensis</italic> induced IL-10 in both cell lines. However, <italic>L. infantum and L. amazonensis</italic> also induced TGF-β in RAW 264.7. CD86 and MHC expression showed that <italic>L. amazonensis</italic> modulated them in both cell lines. Conversely, the parasite load profile did not show significant difference between both macrophage cell lines after 48 h of infection, which suggests that other mechanisms of <italic>Leishmania</italic> control could be involved in DH82 cells.</p>