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PLoS Negl Trop Dis. 2016 Mar 31;10(3):e0004570. doi: 10.1371/journal.pntd.0004570. eCollection 2016 Mar.

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.

Author information

1
Unidad de Investigación en Medicina Experimental, Centro de Medicina Tropical, Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida Universidad 3000, C.P.04510 México, D.F., México.
2
Unidad de Investigación en Medicina Experimental, Centro de Medicina Tropical, Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida, D.F., México.
3
Computational Genomics, Instituto Nacional de Medicina Genómica, Arenal Tepepan, México D.F., México.

Abstract

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.

PMID:
27031998
PMCID:
PMC4816531
DOI:
10.1371/journal.pntd.0004570
[Indexed for MEDLINE]
Free PMC Article

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