Down-Regulation of TLR and JAK/STAT Pathway Genes Is Associated with Diffuse Cutaneous Leishmaniasis: A Gene Expression Analysis in NK Cells from Patients Infected with Leishmania mexicana.

An important NK-cell inhibition with reduced TNF-α, IFN-γ and TLR2 expression had previously been identified in patients with diffuse cutaneous leishmaniasis (DCL) infected with Leishmania mexicana. In an attempt to pinpoint alterations in the signaling pathways responsible for the NK-cell dysfuncti...

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Bibliographic Details
Published in:PLOS Neglected Tropical Diseases
Main Authors: Edith A Fernández-Figueroa, Iván Imaz-Rosshandler, Juan E Castillo-Fernández, Haydee Miranda-Ortíz, Juan C Fernández-López, Ingeborg Becker, Claudia Rangel-Escareño
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2016
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Online Access:https://doi.org/10.1371/journal.pntd.0004570
https://doaj.org/article/2edf093174524b4aa7963486a47de8ea
Description
Summary:An important NK-cell inhibition with reduced TNF-α, IFN-γ and TLR2 expression had previously been identified in patients with diffuse cutaneous leishmaniasis (DCL) infected with Leishmania mexicana. In an attempt to pinpoint alterations in the signaling pathways responsible for the NK-cell dysfunction in patients with DCL, this study aimed at identifying differences in the NK-cell response towards Leishmania mexicana lipophosphoglycan (LPG) between patients with localized and diffuse cutaneous leishmaniasis through gene expression profiling. Our results indicate that important genes involved in the innate immune response to Leishmania are down-regulated in NK cells from DCL patients, particularly TLR and JAK/STAT signaling pathways. This down-regulation showed to be independent of LPG stimulation. The study sheds new light for understanding the mechanisms that undermine the correct effector functions of NK cells in patients with diffuse cutaneous leishmaniasis contributing to a better understanding of the pathobiology of leishmaniasis.