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

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

doi:10.3389/fimmu.2017.01896

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.

Highlights

A dramatic variation of clinical manifestations upon Leishmania infection has been known for many years, suggesting that infection with either more than one species, or variants of the same species of Leishmania parasites leads to distinct clinical outcomes [1,2,3]
Our hypothesis was that if there were differences in the response induced by the different strains, that they could help explain distinct immune responses and subsequent clinical forms observed in human infection with L. braziliensis vs. L. infantum
While there is a range of intensities of CFSE+ Leishmania-infected monocytes between the strains, the percentage of infected monocytes was equivalent between the strains at 4 h following infection (Figure 1) and a very slight difference at 16 h

Summary

Introduction

A dramatic variation of clinical manifestations upon Leishmania infection has been known for many years, suggesting that infection with either more than one species, or variants of the same species of Leishmania parasites leads to distinct clinical outcomes [1,2,3]. While distinct clinical outcomes have been associated with infection by different species of Leishmania, studies have demonstrated that the same parasite species can cause distinct disease manifestations depending on the host [5] and can lead to distinct clinical manifestations in humans due to different strains from the same species [6], as well as differential stimulatory activity in vitro [7]. Different isolates of L. braziliensis have been shown to induce distinct pathology in animal models [8, 9]. These findings have important implications in understanding parasite biology and implicate the host immune response in disease evolution

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Results

Conclusion