title: Role of Toll-like receptor 13 in innate immune recognition of group B streptococci.
abstract: Murine Toll-like receptor 13 (TLR13), an endosomal receptor that is not present in humans, is activated by an unmethylated motif present in the large ribosomal 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 the ErmC methyltransferase, which results in dimethylation of the 23S rRNA motif at a critical adenine residue. We found that TLR13-mediated rRNA recognition was required for optimal induction of tumor necrosis factor alpha and nitrous oxide in dendritic cell and macrophage cultures stimulated with heat-killed bacteria or purified bacterial RNA. However, TLR13-dependent recognition was redundant when live bacteria were used as a stimulus. Moreover, masking bacterial rRNA from TLR13 recognition did not increase the ability of GBS to avoid host defenses and replicate in vivo. In contrast, increased susceptibility to infection was observed under conditions in which signaling by all endosomal TLRs was abolished, i.e., in mice with a loss-of-function mutation in the chaperone protein UNC93B1. Our data lend support to the conclusion that TLR13 participates in GBS recognition, although blockade of the function of this receptor can be compensated for by other endosomal TLRs. Lack of selective pressure by bacterial infections might explain the evolutionary loss of TLR13 in humans. However, further studies using different bacterial species are needed to prove this hypothesis.
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Signorino
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy.
authors.forename: Nastaran
authors.initials: N
authors.lastname: Mohammadi
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Patanè
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Buscetta
authors.affiliation: Dipartimento di Scienze Sperimentali, Medico-Chirurgiche, Specialistiche e Odontostomatologiche, University of Messina, Messina, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Venza
authors.affiliation: Dipartimento di Scienze Sperimentali, Medico-Chirurgiche, Specialistiche e Odontostomatologiche, University of Messina, Messina, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Venza
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancuso
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy.
authors.forename: Angelina
authors.initials: A
authors.lastname: Midiri
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Marseille, France.
authors.forename: Lena
authors.initials: L
authors.lastname: Alexopoulou
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Teti
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy cbiondo@unime.it.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Biondo
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Beninati
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016000:Cluster Analysis; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004275:DNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D003713:Dendritic Cells; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010802:Phylogeny; D012338:RNA, Ribosomal, 23S / Q000276:immunology; D017422:Sequence Analysis, DNA; D013292:Streptococcus agalactiae / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*
chemical_list: D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D012338:RNA, Ribosomal, 23S; C539093:Tlr13 protein, mouse; D051193:Toll-Like Receptors