Recognition of Profilin by Toll-like Receptor 12 Is Critical for Host Resistance to Toxoplasma gondii

Abstract

SUMMARY 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.

Microbial Sensing by Toll-Like Receptors and Intracellular Nucleic Acid Sensors

“…TLRs are broadly classified into two categories depending on their cellular localizations and the PAMPs they recognize. TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are located on the plasma membrane and recognize lipids, lipoproteins, and proteins, whereas TLR3, TLR7, TLR8, TLR9, TLR11, TLR12, and TLR13 are localized in endosomal compartments where they recognize microbial nucleic acids and, under some special conditions (autoimmunity), self-nucleic acids Celhar et al 2012;Oldenburg et al 2012;Koblansky et al 2013). On specific ligand recognition, TLRs activate multiple signaling pathways by recruiting adaptor proteins, which initiate signal transduction pathways that culminate in the activation of transcription factors, such as nuclear factor-kappa B (NF-kB), mitogen-activated protein kinases (MAPKs), and members of the interferon (IFN) regulatory factor family, to regulate the expressions of cytokines, chemokines, and IFNs that eventuate in the host defense to microbial infection.…”

Investigation of Toxoplasma gondii Infection in Cutaneous Leishmaniasis Patients of the Isfahan Province

“…It is an obligate intracellular parasite and proliferates inside host cells as well as macrophages (2). Toxoplasma gondii infects more than 60% of the population worldwide (3). It can infect almost all warm-blooded creatures such as, human, animals, birds and marine mammals (4).…”

Clinical Significance of Toll-Like Receptor and Toll-Like Receptor Blocker

“…TLR12, which is extremely homologous to TLR11, identifies profilin derived from Toxoplasma gondii [31]. The ligand for TLR12 is profilin.…”

“…TLR13 identifies bacterial 23S ribosomal RNA [31,32]. The sequence of bacterial 23S ribosomal RNA found by TLR13 has been recognized as a conserved CGGAAAGACC motif [33].…”