title: NKT cell activation by Leishmania mexicana LPG: Description of a novel pathway.
abstract: NKT cells have been associated with protection against Leishmania donovani, yet their role in infections with Leishmania mexicana has not been addressed, nor has the activation pathway been defined after stimulation with Leishmania mexicana lipophosphoglycan (LPG). We analyzed the activation of NKT cells and their cytokine production in response to Leishmania mexicana LPG. Additionally we compared NKT-cell numbers and cytokine profile in lymph nodes of skin lesions induced by Leishmania mexicana in BALB/c and C57BL/6 mice. We show that LPG activates NKT cells primarily through the indirect pathway, initiating with TLR2 stimulation of dendritic cells (DC), thereby enhancing TLR2, MHC II, and CD86 expressions and IL-12p70 production. This leads to IFN-γ production by NKT cells. C57BL/6 mice showed enhanced DC activation, which correlated with augmented IFN-γ production by NKT cells. Additionally, infected C57BL/6 mice showed elevated percentages of NKT cells with higher IFN-γ and IL-4 production in lymph nodes. We conclude that the response of NKT cells towards Leishmania mexicana LPG initiates with the indirect activation, after binding of LPG to TLR2 in DC. This indirect activation pathway enables NKT cells to produce IFN-γ during the innate phase of Leishmania infection, the magnitude of which differs between mouse strains.
authors: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Hospital General de México, Dr. Balmis 148, Ciudad de Mexico C.P. 06726, Mexico.
authors: Jaime
authors: J
authors: Zamora-Chimal
authors: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Hospital General de México, Dr. Balmis 148, Ciudad de Mexico C.P. 06726, Mexico.
authors: Edith A
authors: EA
authors: Fernández-Figueroa
authors: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Hospital General de México, Dr. Balmis 148, Ciudad de Mexico C.P. 06726, Mexico.
authors: Adriana
authors: A
authors: Ruiz-Remigio
authors: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Hospital General de México, Dr. Balmis 148, Ciudad de Mexico C.P. 06726, Mexico.
authors: Arturo A
authors: AA
authors: Wilkins-Rodríguez
authors: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Hospital General de México, Dr. Balmis 148, Ciudad de Mexico C.P. 06726, Mexico.
authors: José
authors: J
authors: Delgado-Domínguez
authors: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Hospital General de México, Dr. Balmis 148, Ciudad de Mexico C.P. 06726, Mexico.
authors: Norma
authors: N
authors: Salaiza-Suazo
authors: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Hospital General de México, Dr. Balmis 148, Ciudad de Mexico C.P. 06726, Mexico.
authors: Laila
authors: L
authors: Gutiérrez-Kobeh
authors: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Hospital General de México, Dr. Balmis 148, Ciudad de Mexico C.P. 06726, Mexico. Electronic address: becker@unam.mx.
authors: Ingeborg
authors: I
authors: Becker
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006028:Glycosphingolipids / Q000276:immunology*; D006790:Host-Parasite Interactions / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007894:Leishmania mexicana / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D051195:Toll-Like Receptor 2 / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D006028:Glycosphingolipids; D051195:Toll-Like Receptor 2; C008290:lipophosphonoglycan; D007371:Interferon-gamma
keywords: Cytokines; Dendritic cells; LPG; Leishmania mexicana; NKT; TLR2