Article

Contribution of Toll-like receptors to the innate immune response to Gram-negative and Gram-positive bacteria

NovImmune SA, Genève, Geneva, Switzerland
Blood (Impact Factor: 10.45). 03/2007; 109(4):1574-83. DOI: 10.1182/blood-2006-06-032961
Source: PubMed

ABSTRACT

Innate recognition of bacteria is a key step in the activation of inflammation and coagulation, and it is dependent on pathogen-associated molecular pattern (PAMP) ligation to Toll-like receptors (TLRs) and CD14. The dominant receptors activated when cells encounter a whole bacterium, which express several PAMPs, are poorly defined. Herein, we have stimulated various human cells with prototypic Gram-negative and Gram-positive bacteria. Receptor-dependent responses to whole bacteria were assessed using both TLR-transfected cells and specific monoclonal antibodies against TLRs, MD-2, and CD14. Enterobacteria-activated leukocytes and endothelial cells in a TLR4/MD-2-dependent manner, most likely via lipopolysaccharide (LPS). TLR2 activation was observed with a high bacterial inoculum, and in epithelial cells expressing TLR2 but not TLR4. Pseudomonas aeruginosa stimulated cells by both TLR2 and TLR4/MD-2. Gram-positive bacteria activated cells only at high concentrations, in a partially TLR2-dependent but TLR4/MD-2-independent manner. Either TLR or CD14 neutralization blocked activation to all bacterial strains tested with the exception of some Gram-positive strains in whole blood in which partial inhibition was noted. This study identifies dominant TLRs involved in responses to whole bacteria. It also validates the concept that host cell activation by bacterial pathogens can be therapeutically reduced by anti-TLR4, -TLR2, and -CD14 mAbs.

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Available from: Greg Elson, May 23, 2014
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    • "In line, TLR4 expression and LPS reactivity by myeloid cells, B-cells and endothelial cells have been extensively reported (Muzio et al., 1998; Zhang et al., 1999; Elson et al., 2007). In addition, for the first time we demonstrate that sMD-2 release of the MD-2 expressing cells studied in this work was restricted to dendritic and endothelial cells. "

    Full-text · Dataset · May 2014
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    • "In line, TLR4 expression and LPS reactivity by myeloid cells, B-cells and endothelial cells have been extensively reported (Muzio et al., 1998; Zhang et al., 1999; Elson et al., 2007). In addition, for the first time we demonstrate that sMD-2 release of the MD-2 expressing cells studied in this work was restricted to dendritic and endothelial cells. "

    Full-text · Dataset · May 2014
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