Finetunes 064574/8/2023 ![]() Cytosolic PRRs such as cyclic GMP-AMP synthase (cGAS), retinoic acid inducible gene I (RIG-I) and Melanoma Differentiation-Associated protein 5 (MDA5) also sense replication intermediates of numerous viruses. The latter include TLR3, TLR7/8 and TLR9 which recognize double-stranded RNA (dsRNA), single-stranded RNA or CpG-containing DNA, respectively (reviewed in ). One important family of PRRs includes the Toll-like receptors (TLRs) that span cell or endosomal membranes. These pattern recognition receptors (PRR) recognize pathogen-associated molecular pattern (PAMPs), which are highly conserved molecular structures produced by pathogens but not by the host cells. The host immune system offers a variety of different innate receptors to sense invading viruses. Our findings qualify TLR3 as target of immune therapy against retroviral infections. TLR3 mediates antiretroviral cytotoxic NK cell and CD8 + T cell activity in vivo. Moreover, cytotoxicity of natural killer (NK) cells as well as CD8 + T cells were reduced in vitro and in vivo, respectively, in FV-infected TLR3 -/- mice. DCs generated from FV-infected TLR3 −/− mice were less capable of priming virus-specific CD8 + T cell proliferation. TLR3 −/− mice exhibited significantly lower expression levels of type I interferons (IFNs) and IFN-stimulated genes like Pkr or Ifi44, as well as reduced numbers of activated myeloid dendritic cells (DCs) (CD86 + and MHC-II +). Infection of mice deficient in TLR3 (TLR3 −/−) with Friend retrovirus (FV) complex revealed higher viral loads during acute retroviral infection compared to wild type mice. Thus, we considered TLR3 as primer of cell-mediated immunity against retroviruses in vivo. Double-stranded RNA intermediates produced during retroviral replication are good candidates for immune stimulatory viral products. However, the origin of efficient cell-mediated immunity towards retroviruses is unknown. TLR7 mediates host sensing of retroviruses and could significantly influence retrovirus-specific antibody responses. ![]() Specific groups rather than single members of the protein family of pattern recognition receptors (PRRs) such as membrane spanning Toll-like receptors (TLRs) and cytosolic helicases might mediate sensing of replication intermediates of a specific virus species. Pathogen recognition drives host defense towards viral infections.
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