The Immune Response to Trypanosoma cruzi: Role of Toll-Like Receptors and Perspectives for Vaccine Development
T. cruzi-derived PAMPs are recognized by different TLRs. The recognition of different T. cruzi molecules, like parasite surface glycoconjugates and nucleic acids, occurs through distinct Toll-like receptors, which are localized at the cellular plasma or endoplasmic membranes, respectively, and are differentially expressed by various innate immune cell types. GPI anchors of mucin-like glycoproteins activate TLR2/TLR6 heterodimer, GIPL is an agonist for TLR4, genomic DNA activates endosomal TLR9, and TLR7 is involved in parasite RNA recognition. TLRs induce NF-κB and/or IRFs activation via their interaction with different TIR domain-containing adaptor molecules. Of these, MyD88 and Mal/TIRAP are required for TLR2 and TLR4 activation of NF-κB. In a MyD88-independent way, TRIF and TRAM signal downstream TLR4, activating IRF3. TLR7 and TLR9 activate NF-κB and IRF7 via MyD88. NF-κB activation leads to proinflammatory cytokines production, such as TNF-α and IL-12, whereas IRFs are required for type I IFN gene transcription.
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