Source: Annual Congress 2008 - Mechanisms of respiratory infections: interaction between the pathogen and the host
Disease area: Respiratory infections

Abstract

Pulmonary presence of the facultative intracellular pathogen nontypeable Haemophilus influenzae (NTHI) is associated with acute infection and has been implicated as an infectious trigger in chronic obstructive pulmonary disease. In addition NTHI represents a predominant cause of bacterial pneumonia and is able to activate EGFR signaling by NTHI-derived EGF-like factor.
Vital lung specimens were infected with a suspension of 10⁶ colony forming units (cfu) x ml^-1 over a periode of 24h. Presence of NTHI DNA was detected using in situ hybridization (ISH) in in vitro infected lung tissue. CXCL-8 and TNF-α expression was determined by ELISA. Toll-like receptor- (TLR) 2 mRNA was analyzed by realtime-PCR. Expression of the MAP-Kinases p38 and p42/44 was determined by western blot.
NTHI DNA was found to be located in 60-75% of alveolar macrophages (AM) and 15-25% of epithelial cells (AEC) in in vitro infected lung tissues (n=18).
NTHI infection increased TLR2 mRNA expression and induced a strong release of CXCL-8 (NTHI 325±170 vs. control 55±43 μg/ml) and TNF-α (NTHI 304±190 vs. control 39±28 pg/ml) in in vitro infected lung specimens (p<0.01). In addition increased expression of the MAP-Kinases p38 and p42/44 was observed after infection. Blockade of TLR2 and EGFR by monoclonal antibody as well as specific inhibition of the MAP Kinases by SB203580 and UO126 significantly decreased the proinflammatory cytokine response.
In conclusion AM and AEC serve as host cells for primary NTHI infection. The strong proinflammatory cytokine expression in human lung tissue is by mediated by TLR2 and EGFR via the p38 and p42/44 MAP-Kinase pathway.

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Citations should be made in the following way:
D. Droemann, J. Rupp, T. Goldmann, F. Xu, S. Limmer, P. Zabel, K. Dalhoff (Lübeck, Borstel, Germany). Nontypeable Haemophilus influenzae infection of human lung tissue induces proinflammatory cytokine response via toll-like receptor 2 and EGF-receptor. Eur Respir J 2008; 32: Suppl. 52, 2283

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