AUTHOR=Viana Agostinho Gonçalves , Magalhães Luísa Mourão Dias , Giunchetti Rodolfo Cordeiro , Dutra Walderez O. , Gollob Kenneth J. 

TITLE=Infection of Human Monocytes with Leishmania infantum Strains Induces a Downmodulated Response when Compared with Infection with Leishmania braziliensis

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01896

DOI=10.3389/fimmu.2017.01896

ISSN=1664-3224

ABSTRACT=<p>Human infection with different species of <italic>Leishmania</italic> leads to distinct clinical manifestations, ranging from relatively mild cutaneous (<italic>Leishmania</italic> braziliensis) to severe visceral (<italic>Leishmania infantum</italic>) forms of leishmaniasis. Here, we asked whether <italic>in vitro</italic> infection of human monocytes by <italic>Leishmania</italic> strains responsible for distinct clinical manifestations leads to early changes in immunological characteristics and ability of the host cells to control <italic>Leishmania</italic>. We evaluated the expression of toll-like receptors and MHC class II molecules, cytokines, and <italic>Leishmania</italic> control by human monocytes following short-term infection with <italic>L. braziliensis</italic> (M2904), a reference strain of <italic>L. infantum</italic> (BH46), and a wild strain of <italic>L. infantum</italic> (wild). The induction of TLR2, TLR9, and HLA-DR were all lower in <italic>L. infantum</italic> when compared with <italic>L. braziliensis</italic>-infected cells. Moreover, <italic>L. infantum</italic>-infected monocytes (both strains) produced lower TNF-alpha and a lower TNF-alpha/IL-10 ratio, resulting in a weaker inflammatory profile and a 100-fold less effective control of <italic>Leishmania</italic> than cells infected with <italic>L. braziliensis</italic>. Our results show that <italic>L. infantum</italic> strains fail to induce a strong inflammatory response, less activation, and less control of <italic>Leishmania</italic> from human monocytes, when compared with that induced by <italic>L. braziliensis</italic> infection. This functional profile may help explain the distinct clinical course observed in patients infected with the different <italic>Leishmania</italic> species.</p>