title: Recognition of profilin by Toll-like receptor 12 is critical for host resistance to Toxoplasma gondii.
abstract: Toll-like receptor 11 (TLR11) recognizes T. gondii profilin (TgPRF) and is required for interleukin-12 production and induction of immune responses that limit cyst burden in Toxoplasma gondii-infected mice. However, TLR11 only modestly affects survival of T. gondii-challenged mice. We report that TLR12, a previously uncharacterized TLR, also recognized TgPRF. TLR12 was sufficient for recognition of TgPRF by plasmacytoid dendritic cells (pDCs), whereas TLR11 and TLR12 were both required in macrophages and conventional DCs. In contrast to TLR11, TLR12-deficient mice succumb rapidly to T. gondii infection. TLR12-dependent induction of IL-12 and IFN-α in pDCs led to production of IFN-γ by NK cells. Consistent with this observation, the partial resistance of Tlr11(-/-) mice is lost upon pDC or NK cell depletion. Thus, TLR12 is critical for the innate immune response to T. gondii, and this TLR may promote host resistance by triggering pDC and NK cell function.
authors.affiliation: Department of Microbiology & Immunology, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: A Alicia
authors.initials: AA
authors.lastname: Koblansky
authors.forename: Dragana
authors.initials: D
authors.lastname: Jankovic
authors.forename: Hyunju
authors.initials: H
authors.lastname: Oh
authors.forename: Sara
authors.initials: S
authors.lastname: Hieny
authors.forename: Waradon
authors.initials: W
authors.lastname: Sungnak
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Mathur
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Hayden
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Alan
authors.initials: A
authors.lastname: Sher
authors.forename: Sankar
authors.initials: S
authors.lastname: Ghosh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D054884:Host-Pathogen Interactions / Q000276:immunology*; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D051304:Profilins / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D016415:Sequence Alignment; D051193:Toll-Like Receptors / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016898:Interferon-alpha; D016328:NF-kappa B; D051304:Profilins; C482903:Tlr11 protein, mouse; C539092:Tlr12 protein, mouse; D051193:Toll-Like Receptors; D018664:Interleukin-12; D007371:Interferon-gamma