title: 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.
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.
authors.affiliation: Department of Microbiology, The Ohio State University, Columbus, Ohio, United States.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Tuladhar
authors.affiliation: Department of Oral Biology, The Ohio State University, Columbus, Ohio, United States; Department of Pathology, The Ohio State University, Columbus, Ohio, United States.
authors.forename: Steve
authors.initials: S
authors.lastname: Oghumu
authors.affiliation: Department of Microbiology, The Ohio State University, Columbus, Ohio, United States.
authors.forename: Ran
authors.initials: R
authors.lastname: Dong
authors.affiliation: Brigham and Woman's Hospital, Harvard Medical Centre, Boston, Massachusetts, United States.
authors.forename: Allison
authors.initials: A
authors.lastname: Peterson
authors.affiliation: Brigham and Woman's Hospital, Harvard Medical Centre, Boston, Massachusetts, United States.
authors.forename: Arlene H
authors.initials: AH
authors.lastname: Sharpe
authors.affiliation: Department of Microbiology, The Ohio State University, Columbus, Ohio, United States; Department of Oral Biology, The Ohio State University, Columbus, Ohio, United States; Department of Pathology, The Ohio State University, Columbus, Ohio, United States. Electronic address: Abhay.Satoskar@osumc.edu.
authors.forename: Abhay R
authors.initials: AR
authors.lastname: Satoskar
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D016207:Cytokines / Q000097:blood; D005260:Female; D018320:Leishmania major / Q000276:immunology / Q000472:pathogenicity; D007894:Leishmania mexicana / Q000276:immunology / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D053278:OX40 Ligand / Q000276:immunology / Q000378:metabolism*; D053262:Receptors, OX40 / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*; D014774:Virulence
chemical_list: D000913:Antibodies, Protozoan; D016207:Cytokines; D053278:OX40 Ligand; D053262:Receptors, OX40
keywords: Cutaneous leishmaniasis; L. major; L. mexicana; Ox40L–Ox40