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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.

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.
AuthorsEdith A Fernández-Figueroa, Iván Imaz-Rosshandler, Juan E Castillo-Fernández, Haydee Miranda-Ortíz, Juan C Fernández-López, Ingeborg Becker, Claudia Rangel-Escareño
JournalPLoS neglected tropical diseases (PLoS Negl Trop Dis) Vol. 10 Issue 3 Pg. e0004570 (Mar 2016) ISSN: 1935-2735 [Electronic] United States
PMID27031998 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • STAT Transcription Factors
  • Toll-Like Receptors
  • Janus Kinases
Topics
  • Down-Regulation
  • Gene Expression Regulation (physiology)
  • Humans
  • Janus Kinases (genetics, metabolism)
  • Killer Cells, Natural (physiology)
  • Leishmania mexicana
  • Leishmaniasis, Diffuse Cutaneous (metabolism)
  • STAT Transcription Factors (genetics, metabolism)
  • Signal Transduction (physiology)
  • Toll-Like Receptors (metabolism)
  • Transcriptome

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