RGD Reference Report - Altered inflammatory responses in TLR5-deficient mice infected with Legionella pneumophila. - Rat Genome Database

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Altered inflammatory responses in TLR5-deficient mice infected with Legionella pneumophila.

Authors: Hawn, TR  Berrington, WR  Smith, IA  Uematsu, S  Akira, S  Aderem, A  Smith, KD  Skerrett, SJ 
Citation: Hawn TR, etal., J Immunol. 2007 Nov 15;179(10):6981-7.
RGD ID: 5129510
Pubmed: PMID:17982089   (View Abstract at PubMed)

Legionella pneumophila (Lp), an important cause of morbidity and mortality from pneumonia, infects alveolar macrophages (AMs) and is recognized by several TLRs as well as Birc1e (NAIP5) and IL-1 converting enzyme-protease activating factor. We examined the role of TLR5 during the murine response to aerosolized Lp infection. At 4 h after infection, Tlr5(-/-) mice had lower numbers of polymorphonuclear neutrophils (PMNs) in their broncho-alveolar lavage fluid in comparison to wild-type (WT) mice. At 24 and 72 h, the PMN recruitment was similar. WT mice infected with a flagellin-deficient strain (LpFlaA-) also showed an impaired early PMN response at 4 h compared with those infected with the WT strain. There was no consistent difference in bacterial counts at any of the time points when comparing the Tlr5(-/-) and WT mice. However, at 6 days after infection, the Tlr5(-/-) mice had increased leukocytic infiltrates in the alveolar and peribronchial interstitial spaces that were consistent with organizing pneumonia. We also examined the role of TLR5 during macrophage infection. In contrast to bone marrow-derived macrophages, AMs secreted TNF-alpha after stimulation with purified flagellin. In addition, WT, but not Tlr5(-/-), AMs produced TNF-alpha after stimulation with Lp. Live LpFlaA- did not induce TNF-alpha secretion in AM. These results suggested that AMs recognize Lp flagellin and that a majority of the Lp-induced TNF-alpha response is TLR5-mediated. Thus, TLR5 mediates recognition of Lp in AMs and performs a distinct role during the in vivo pulmonary immune response through regulation of early PMN recruitment and subsequent later development of pneumonia.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TLR5HumanLegionnaires' disease  ISOTlr5 (Mus musculus) RGD 
Tlr5RatLegionnaires' disease  ISOTlr5 (Mus musculus) RGD 
Tlr5MouseLegionnaires' disease  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tlr5  (toll-like receptor 5)

Genes (Mus musculus)
Tlr5  (toll-like receptor 5)

Genes (Homo sapiens)
TLR5  (toll like receptor 5)


Additional Information