title: 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.
authors.affiliation: 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.
authors.forename: Edith A
authors.initials: EA
authors.lastname: Fernández-Figueroa
authors.affiliation: Unidad de Investigación en Medicina Experimental, Centro de Medicina Tropical, Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida, D.F., México.
authors.forename: Iván
authors.initials: I
authors.lastname: Imaz-Rosshandler
authors.affiliation: Unidad de Investigación en Medicina Experimental, Centro de Medicina Tropical, Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida, D.F., México.
authors.forename: Juan E
authors.initials: JE
authors.lastname: Castillo-Fernández
authors.affiliation: Unidad de Investigación en Medicina Experimental, Centro de Medicina Tropical, Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida, D.F., México.
authors.forename: Haydee
authors.initials: H
authors.lastname: Miranda-Ortíz
authors.affiliation: Unidad de Investigación en Medicina Experimental, Centro de Medicina Tropical, Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida, D.F., México.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Fernández-López
authors.affiliation: Computational Genomics, Instituto Nacional de Medicina Genómica, Arenal Tepepan, México D.F., México.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Becker
authors.affiliation: Unidad de Investigación en Medicina Experimental, Centro de Medicina Tropical, Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida, D.F., México.
authors.forename: Claudia
authors.initials: C
authors.lastname: Rangel-Escareño
mesh_terms: D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000502:physiology*; D007894:Leishmania mexicana; D016774:Leishmaniasis, Diffuse Cutaneous / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051193:Toll-Like Receptors / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D050791:STAT Transcription Factors; D051193:Toll-Like Receptors; D053612:Janus Kinases