title: Type III secretion needle proteins induce cell signaling and cytokine secretion via Toll-like receptors.
abstract: Pathogens are recognized by hosts by use of various receptors, including the Toll-like receptor (TLR) and Nod-like receptor (NLR) families. Ligands for these varied receptors, including bacterial products, are identified by the immune system, resulting in development of innate immune responses. Only a couple of components from type III secretion (T3S) systems are known to be recognized by TLR or NLR family members. Known T3S components that are detected by pattern recognition receptors (PRRs) are (i) flagellin, detected by TLR5 and NLRC4 (Ipaf); and (ii) T3S rod proteins (PrgJ and homologs) and needle proteins (PrgI and homologs), detected by NAIP and the NLRC4 inflammasome. In this report, we characterize the induction of proinflammatory responses through TLRs by the Yersinia pestis T3S needle protein, YscF, the Salmonella enterica needle proteins PrgI and SsaG, and the Shigella needle protein, MxiH. More specifically, we determine that the proinflammatory responses occur through TLR2 and -4. These data support the hypothesis that T3S needles have an unrecognized role in bacterial pathogenesis by modulating immune responses.
authors.affiliation: Department of Basic Sciences, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, North Dakota, USA.
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Jessen
authors.forename: Patrick
authors.initials: P
authors.lastname: Osei-Owusu
authors.forename: Melody
authors.initials: M
authors.lastname: Toosky
authors.forename: William
authors.initials: W
authors.lastname: Roughead
authors.forename: David S
authors.initials: DS
authors.lastname: Bradley
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Nilles
mesh_terms: D058947:Bacterial Secretion Systems / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism*; D004926:Escherichia coli / Q000502:physiology; D029968:Escherichia coli Proteins / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology*; D051193:Toll-Like Receptors / Q000502:physiology*
chemical_list: D058947:Bacterial Secretion Systems; D016207:Cytokines; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D051193:Toll-Like Receptors