Leishmania mexicana lipophosphoglycan activates ERK and p38 MAP kinase and induces production of proinflammatory cytokines in human macrophages through TLR2 and TLR4
Por:
Rojas-Bernabé A., Garcia-Hernández O., Maldonado-Bernal C., Delegado-Dominguez J., Ortega E., Gutiérrez-Kobeh L., Becker I., Aguirre-Garcia M.
Publicada:
1 may 2014
Resumen:
Protozoan parasites of genus Leishmania are the causative agents of leishmaniasis. Leishmania promastigotes primarily infect macrophages in the host, where they transform into amastigotes and multiply. Lipophosphoglycan (LPG), the most abundant surface molecule of the parasite, is a virulence determinant that regulates the host immune response. Promastigotes are able to modulate this effect through LPG, creating a favourable environment for parasite survival, although the mechanisms underlying this modulation remain unknown. We analysed the participation of TLR2 and TLR4 in the production of cytokines and explored the possible phosphorylation of ERK and/or p38 MAP kinase signalling cascades in human macrophages stimulated with Leishmania mexicana LPG. The results show that LPG induced the production of TNF-a, IL-1ß, IL-12p40, IL-12p70 and IL-10 and led to phosphorylation of ERK and p38 MAP kinase. Specific inhibitors of ERK or p38 MAP kinases and mAbs against TLR2 and TLR4 reduced cytokine production and phosphorylation of both kinases. Our results suggest that L. mexicana LPG binds TLR2 and TLR4 receptors in human macrophages, leading to ERK and MAP kinase phosphorylation and production of pro-inflammatory cytokines. © 2014 Cambridge University Press.
Filiaciones:
Rojas-Bernabé A.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Mexico City 06726, DF, Mexico
Garcia-Hernández O.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Mexico City 06726, DF, Mexico
Maldonado-Bernal C.:
Unidad de Investigación de Enfermedades Oncológicas, Hospital Infantil de México Federico Gómez, México, DF, Mexico
Delegado-Dominguez J.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Mexico City 06726, DF, Mexico
Ortega E.:
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, DF, Mexico
Gutiérrez-Kobeh L.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Mexico City 06726, DF, Mexico
Becker I.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Mexico City 06726, DF, Mexico
Aguirre-Garcia M.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Mexico City 06726, DF, Mexico
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