Ox40L-Ox40 pathway plays distinct roles in regulating Th2 responses but does not determine outcome of cutaneous leishmaniasis caused by Leishmania mexicana and Leishmania major

Exp Parasitol. 2015 Jan:148:49-55. doi: 10.1016/j.exppara.2014.11.002. Epub 2014 Nov 11.

Abstract

Ox40 ligand (Ox40L)-Ox40 pathway has been shown to enhance Th2 responses and play a role in pathogenesis of cutaneous leishmaniasis (CL) caused by Leishmania major. Using Ox40l(-/-) BALB/c mice we analyzed the role of this pathway in determining the outcome to CL caused by L. mexicana and compared to L. major. Contrary to our expectations, Ox40l(-/-) mice were highly susceptible to both L. major (LV39) and L. mexicana (M379) and developed large non-healing lesions containing parasites comparable to Ox40l(+/+) BALB/c mice. Interestingly, upon in vitro stimulation with Leishmania antigen (LmAg), the lymph node cells from L. major infected Ox40l(-/-) mice produced significantly less IL-4 and IL-10 compared to Ox40l(+/+) mice. L. mexicana infected Ox40l(-/-) and Ox40l(+/+) mice did not show any difference in the production of IL-4 and IL-10. No difference was noted in the amount of Th1 cytokines IFN-ү and IL-12 produced by Ox40l(-/-) and Ox40l(+/+) mice infected with either parasite. These results indicate that the Ox40L-Ox40 pathway promotes Th2 bias only in L. major infection but not L. mexicana infection and this pathway is not critical for susceptibility to CL.

Keywords: Cutaneous leishmaniasis; L. major; L. mexicana; Ox40L–Ox40.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Protozoan / blood
  • Cytokines / blood
  • Female
  • Leishmania major* / immunology
  • Leishmania major* / pathogenicity
  • Leishmania mexicana* / immunology
  • Leishmania mexicana* / pathogenicity
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / parasitology
  • Leishmaniasis, Cutaneous / pathology
  • Mice
  • Mice, Inbred BALB C
  • OX40 Ligand / immunology
  • OX40 Ligand / metabolism*
  • Receptors, OX40 / immunology
  • Receptors, OX40 / metabolism*
  • Th2 Cells / immunology
  • Th2 Cells / metabolism*
  • Virulence

Substances

  • Antibodies, Protozoan
  • Cytokines
  • OX40 Ligand
  • Receptors, OX40