Murine TLR13, an endosomal receptor that is not present in humans, is activated by an unmethylated motif present in the large ribosome subunit of bacterial RNA (23S rRNA). Little is known, however, of the impact of TLR13 on antibacterial host defenses. Here we examined the role of this receptor in the context of infection induced by the model pathogen group B Streptococcus (GBS). To this end, we used bacterial strains masked from TLR13 recognition by virtue of constitutive expression of ermC methyltransferase, which results in dimethylation of the 23S rRNA motif at a critical adenine residue. We found that TLR13-mediated rRNA recognition is required for optimal induction of tumor necrosis factor-α and nitrous oxide in dendritic cell and macrophage cultures stimulated with heat killed bacteria 33 or purified bacterial RNA. However, TLR13-dependent recognition was redundant when using live 34 bacteria as a stimulus. Moreover, masking bacterial rRNA from TLR13 recognition did not increase the 35 ability of GBS to avoid host defenses and replicate in vivo. In contrast, increased susceptibility to 36 infection was observed under conditions in which signaling by all endosomal TLRs is abolished i.e. in 37 mice with a loss-of-function mutation in the chaperone protein UNC93B1. Our data lend support to the 38 conclusion that TLR13 participates in GBS recognition, although blockade of the function of this 39 receptor can be compensated for by other endosomal TLRs. Lack of selective pressure by bacterial 40 infections might explain the evolutionary loss of TLR13 in humans. However, further studies using 41 different bacterial species are needed to prove this hypothesis.

Role of TLR13 in innate immune recognition of group B streptococci

MOHAMMADI, NASTARAN;PATANE', FRANCESCO;VENZA, Mario;VENZA, Isabella;MANCUSO, Giuseppe;MIDIRI, Angelina;TETI, Giuseppe;BIONDO, Carmelo;BENINATI, Concetta
2014-01-01

Abstract

Murine TLR13, an endosomal receptor that is not present in humans, is activated by an unmethylated motif present in the large ribosome subunit of bacterial RNA (23S rRNA). Little is known, however, of the impact of TLR13 on antibacterial host defenses. Here we examined the role of this receptor in the context of infection induced by the model pathogen group B Streptococcus (GBS). To this end, we used bacterial strains masked from TLR13 recognition by virtue of constitutive expression of ermC methyltransferase, which results in dimethylation of the 23S rRNA motif at a critical adenine residue. We found that TLR13-mediated rRNA recognition is required for optimal induction of tumor necrosis factor-α and nitrous oxide in dendritic cell and macrophage cultures stimulated with heat killed bacteria 33 or purified bacterial RNA. However, TLR13-dependent recognition was redundant when using live 34 bacteria as a stimulus. Moreover, masking bacterial rRNA from TLR13 recognition did not increase the 35 ability of GBS to avoid host defenses and replicate in vivo. In contrast, increased susceptibility to 36 infection was observed under conditions in which signaling by all endosomal TLRs is abolished i.e. in 37 mice with a loss-of-function mutation in the chaperone protein UNC93B1. Our data lend support to the 38 conclusion that TLR13 participates in GBS recognition, although blockade of the function of this 39 receptor can be compensated for by other endosomal TLRs. Lack of selective pressure by bacterial 40 infections might explain the evolutionary loss of TLR13 in humans. However, further studies using 41 different bacterial species are needed to prove this hypothesis.
2014
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/2833372
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