title: Role of Toll-like receptor 9 signaling in experimental Leishmania braziliensis infection.
abstract: Infection with Leishmania braziliensis causes cutaneous or mucocutaneous leishmaniasis in humans. Toll-like receptor 9 (TLR9) expression has been found in granulomas of lesions in L. braziliensis-infected individuals. L. braziliensis inoculation in mice induces very small lesions that are self-healing, whereas deficiency in the TLR adaptor molecule, MyD88, renders mice susceptible to infection. The TLR involved has not been identified, prompting us to investigate if TLR9 triggering by the parasite contributes to the strong resistance to infection observed in L. braziliensis-inoculated mice. The parasites activated wild-type (WT) dendritic cells (DCs) in vitro but not DCs derived from TLR9(-/-) mice. TLR9(-/-) mice inoculated with L. braziliensis exhibited a transient susceptibility characterized by increased lesion size and parasite burden compared to those of WT mice. Surprisingly, elevated levels of gamma interferon (IFN-γ) were measured at the site of infection and in draining lymph node T cells of TLR9(-/-) mice at the peak of susceptibility, suggesting that unlike observations in vitro, the parasite could induce DC activation leading to the development of Th1 cells in the absence of TLR9 expression. Taken together, these data show that TLR9 signaling is important for the early control of lesion development and parasite burden but is dispensable for the differentiation of Th1 cells secreting IFN-γ, and the high levels of this cytokine are not sufficient to control early parasite replication following L. braziliensis infection.
authors: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors: Tiffany
authors: T
authors: Weinkopff
authors: Anita
authors: A
authors: Mariotto
authors: Gregoire
authors: G
authors: Simon
authors: Yazmin
authors: Y
authors: Hauyon-La Torre
authors: Floriane
authors: F
authors: Auderset
authors: Steffen
authors: S
authors: Schuster
authors: Haroun
authors: H
authors: Zangger
authors: Nicolas
authors: N
authors: Fasel
authors: Aldina
authors: A
authors: Barral
authors: Fabienne
authors: F
authors: Tacchini-Cottier
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007892:Leishmania braziliensis; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000172:deficiency / Q000502:physiology*
chemical_list: D016207:Cytokines; D051217:Toll-Like Receptor 9