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
Por:
Fernández-Figueroa E.A., Imaz-Rosshandler I., Castillo-Fernández J.E., Miranda-Ortíz H., Fernández-López J.C., Becker I., Rangel-Escareño C.
Publicada:
1 mar 2016
Resumen:
An important NK-cell inhibition with reduced TNF-alpha, IFN-gamma 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.
Filiaciones:
Fernández-Figueroa E.A.:
Inst Nacl Med Genom, Computat Genom, Mexico City, DF, Mexico
Computational Genomics, Instituto Nacional de Medicina Genómica, Arenal Tepepan D.F, Mexico
Imaz-Rosshandler I.:
Univ Nacl Autonoma Mexico, Fac Med, Ctr Med Trop, Unidad Invest Med Expt, Ave, Mexico City 04510, DF, Mexico
Unidad de Investigación en Medicina Experimental, Centro de Medicina Tropical, Universidad Nacional Autónoma de México, Avenida, D.F, Mexico
Castillo-Fernández J.E.:
Univ Nacl Autonoma Mexico, Fac Med, Ctr Med Trop, Unidad Invest Med Expt, Ave, Mexico City 04510, DF, Mexico
Unidad de Investigación en Medicina Experimental, Centro de Medicina Tropical, Universidad Nacional Autónoma de México, Avenida, D.F, Mexico
Miranda-Ortíz H.:
Univ Nacl Autonoma Mexico, Fac Med, Ctr Med Trop, Unidad Invest Med Expt, Ave, Mexico City 04510, DF, Mexico
Unidad de Investigación en Medicina Experimental, Centro de Medicina Tropical, Universidad Nacional Autónoma de México, Avenida, D.F, Mexico
Fernández-López J.C.:
Univ Nacl Autonoma Mexico, Fac Med, Ctr Med Trop, Unidad Invest Med Expt, Ave, Mexico City 04510, DF, Mexico
Unidad de Investigación en Medicina Experimental, Centro de Medicina Tropical, Universidad Nacional Autónoma de México, Avenida, D.F, Mexico
Becker I.:
Inst Nacl Med Genom, Computat Genom, Mexico City, DF, Mexico
Computational Genomics, Instituto Nacional de Medicina Genómica, Arenal Tepepan D.F, Mexico
Rangel-Escareño C.:
Univ Nacl Autonoma Mexico, Fac Med, Ctr Med Trop, Unidad Invest Med Expt, Ave, Mexico City 04510, DF, Mexico
Unidad de Investigación en Medicina Experimental, Centro de Medicina Tropical, Universidad Nacional Autónoma de México, Avenida, D.F, Mexico
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