RGD Reference Report - Importance of TLR2 in early innate immune response to acute pulmonary infection with Porphyromonas gingivalis in mice. - Rat Genome Database

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Importance of TLR2 in early innate immune response to acute pulmonary infection with Porphyromonas gingivalis in mice.

Authors: Hajishengallis, G  Wang, M  Bagby, GJ  Nelson, S 
Citation: Hajishengallis G, etal., J Immunol. 2008 Sep 15;181(6):4141-9.
RGD ID: 4145337
Pubmed: PMID:18768871   (View Abstract at PubMed)
PMCID: PMC2625304   (View Article at PubMed Central)

The periodontal pathogen Porphyromonas gingivalis is implicated in certain systemic diseases including atherosclerosis and aspiration pneumonia. This organism induces innate responses predominantly through TLR2, which also mediates its ability to induce experimental periodontitis and accelerate atherosclerosis. Using a validated mouse model of intratracheal challenge, we investigated the role of TLR2 in the control of P. gingivalis acute pulmonary infection. TLR2-deficient mice elicited reduced proinflammatory or antimicrobial responses (KC, MIP-1alpha, TNF-alpha, IL-6, IL-12p70, and NO) in the lung and exhibited impaired clearance of P. gingivalis compared with normal controls. However, the influx of polymorphonuclear leukocytes into the lung and the numbers of resident alveolar macrophages (AM) were comparable between the two groups. TLR2 signaling was important for in vitro killing of P. gingivalis by polymorphonuclear leukocytes or AM and, moreover, the AM bactericidal activity required NO production. Strikingly, AM were more potent than peritoneal or splenic macrophages in P. gingivalis killing, attributed to diminished AM expression of complement receptor-3 (CR3), which is exploited by P. gingivalis to promote its survival. The selective expression of CR3 by tissue macrophages and the requirement of TLR2 inside-out signaling for CR3 exploitation by P. gingivalis suggest that the role of TLR2 in host protection may be contextual. Thus, although TLR2 may mediate destructive effects, as seen in models of experimental periodontitis and atherosclerosis, we have now shown that the same receptor confers protection against P. gingivalis in acute lung infection.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TLR2Humanbacterial pneumonia  ISOTlr2 (Mus musculus) RGD 
Tlr2Ratbacterial pneumonia  ISOTlr2 (Mus musculus) RGD 
Tlr2Mousebacterial pneumonia  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tlr2  (toll-like receptor 2)

Genes (Mus musculus)
Tlr2  (toll-like receptor 2)

Genes (Homo sapiens)
TLR2  (toll like receptor 2)


Additional Information