title: Patency of Litomosoides sigmodontis infection depends on Toll-like receptor 4 whereas Toll-like receptor 2 signalling influences filarial-specific CD4(+) T-cell responses.
abstract: BALB/c mice develop a patent state [release of microfilariae (Mf), the transmission life-stage, into the periphery] when exposed to the rodent filariae Litomosoides sigmodontis. Interestingly, only a portion of the infected mice become patent, which reflects the situation in human individuals infected with Wuchereria bancrofti. Since those individuals had differing filarial-specific profiles, this study compared differences in immune responses between Mf(+) and Mf(-) infected BALB/c mice. We demonstrate that cultures of total spleen or mediastinal lymph node cells from Mf(+) mice produce significantly more interleukin-5 (IL-5) to filarial antigens but equal levels of IL-10 when compared with Mf(-) mice. However, isolated CD4(+) T cells from Mf(+) mice produced significantly higher amounts of all measured cytokines, including IL-10, when compared with CD4(+) T-cell responses from Mf(-) mice. Since adaptive immune responses are influenced by triggering the innate immune system we further studied the immune profiles and parasitology in infected Toll-like receptor-2-deficient (TLR2(-/-)) and TLR4(-/-) BALB/c mice. Ninety-three per cent of L. sigmodontis-exposed TLR4(-/-) BALB/c mice became patent (Mf(+)) although worm numbers remained comparable to those in Mf(+) wild-type controls. Lack of TLR2 had no influence on patency outcome or worm burden but infected Mf(+) mice had significantly lower numbers of Foxp3(+) regulatory T cells and dampened peripheral immune responses. Interestingly, in vitro culturing of CD4(+) T cells from infected wild-type mice with granulocyte-macrophage colony-stimulating factor-derived TLR2(-/-) dendritic cells resulted in an overall diminished cytokine profile to filarial antigens. Hence, triggering TLR4 or TLR2 during chronic filarial infection has a significant impact on patency and efficient CD4(+) T-cell responses, respectively.
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital of Bonn, Bonn, Germany.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Rodrigo
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital of Bonn, Bonn, Germany.
authors.forename: Sandy
authors.initials: S
authors.lastname: Schulz
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital of Bonn, Bonn, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Krupp
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital of Bonn, Bonn, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ritter
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital of Bonn, Bonn, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Wiszniewsky
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital of Bonn, Bonn, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Arndts
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital of Bonn, Bonn, Germany.
authors.forename: Ruth S E
authors.initials: RS
authors.lastname: Tamadaho
authors.affiliation: Institute for Molecular Medicine, University Hospital of Bonn, Bonn, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Endl
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital of Bonn, Bonn, Germany.|German Centre for Infection Research (DZIF), Partner Site, Bonn-Cologne, Bonn, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital of Bonn, Bonn, Germany.|German Centre for Infection Research (DZIF), Partner Site, Bonn-Cologne, Bonn, Germany.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Layland
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005368:Filariasis / Q000276:immunology* / Q000469:parasitology; D005370:Filarioidea / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
keywords: Litomosoides sigmodontis; Toll-like receptor 2; Toll-like receptor 4; cytokines; immune regulation; microfilariae