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Front Immunol. 2018 Jan 8;8:1896. doi: 10.3389/fimmu.2017.01896. eCollection 2017.

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

Author information

1
Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
2
Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais (INCT-DT), Belo Horizonte, Brazil.
3
Núcleo de Ensino e Pesquisa, Instituto Mario Penna, Belo Horizonte, Brazil.
4
International Center for Research, AC Camargo Cancer Center, São Paulo, Brazil.

Abstract

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

KEYWORDS:

Leishmania; costimulatory molecules; cytokines; monocytes; pathogen immunity; protozoan parasites

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