title: Signals triggered by a bacterial pore-forming toxin contribute to toll-like receptor redundancy in gram-positive bacterial recognition.
abstract: BACKGROUND
  Toll-like receptor (TLR) 2 is the principal recognition receptor for gram-positive microbes. However, in some gram-positive bacterial infections, TLR2 is dispensable. One of the outstanding questions regarding host-bacteria interactions is why TLR2 is essential in some infections but dispensable in others.
  
  
  METHODS
  We used a combination of bacterial plating, flow cytometry, enzyme-linked immunosorbent assay, and reverse-transcriptase polymerase chain reaction to analyze the inflammatory responses induced by Listeria monocytogenes and its toxin listeriolysin O (LLO) in vitro and in vivo. We analyzed wild-type, TLR2(-/-)-, TLR4(-/-)-, MyD88(-/-)-, interleukin (IL)-1beta(-/-)-, and IL-18(-/-)-deficient mice and the bone marrow-derived mast cells obtained from these respective groups.
  
  
  RESULTS
  TLR2(-/-) mice had unaltered L. monocytogenes clearance and did not experience impairment of cytokine/chemokine induction and neutrophil mobilization by L. monocytogenes or purified LLO, but they were unresponsive to the LLO-deficient mutant L. monocytogenes (LmDeltahly). We show that L. monocytogenes and LLO mediate such responses in part via interleukin (IL)-1beta and IL-18-MyD88 pathways.
  
  
  CONCLUSIONS
  The results illustrate that signals triggered by LLO contribute to TLR2 redundancy in recognition of L. monocytogenes. Under normal conditions, multiple and, sometimes, redundant pathways cooperate to induce a rapid antimicrobial defense. When one signaling pathway-in this case, TLR2-is removed from the system, the other pathways are still capable of mounting a sufficient response to ensure survival of the host.
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany. Nelson.Gekara@helmholtz-hzi.de
authors.forename: Nelson O
authors.initials: NO
authors.lastname: Gekara
authors.forename: Nicole
authors.initials: N
authors.lastname: Dietrich
authors.forename: Marcin
authors.initials: M
authors.lastname: Lyszkiewicz
authors.forename: Stefan
authors.initials: S
authors.lastname: Lienenklaus
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weiss
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D001853:Bone Marrow / Q000502:physiology; D017931:DNA Primers; D006360:Heat-Shock Proteins / Q000633:toxicity*; D006460:Hemolysin Proteins / Q000633:toxicity*; D007249:Inflammation / Q000382:microbiology; D020382:Interleukin-18 / Q000172:deficiency / Q000235:genetics; D053583:Interleukin-1beta / Q000172:deficiency / Q000235:genetics; D008089:Listeria monocytogenes / Q000302:isolation & purification*; D008088:Listeriosis / Q000235:genetics / Q000503:physiopathology*; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000172:deficiency* / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000172:deficiency* / Q000235:genetics
chemical_list: D001427:Bacterial Toxins; D017931:DNA Primers; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D020382:Interleukin-18; D053583:Interleukin-1beta; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C038705:hlyA protein, Listeria monocytogenes