Differential activation of inflammatory pathways in A549 type II pneumocytes by <it>Streptococcus pneumoniae </it>strains with different adherence properties

• Main Authors: Horvat Rebecca T, Reed Natalie A, Robson Rachel L
• Format: Article
• Language: English
• Published: BMC 2006-04-01
• Series: BMC Infectious Diseases
• Online Access: http://www.biomedcentral.com/1471-2334/6/71

<p>Abstract</p> <p>Background</p> <p>Adherence of <it>Streptococcus pneumoniae </it>bacteria to lung cells is a first step in the progression from asymptomatic carriage to pneumonia. Adherence abilities vary widely among <it>S. pneumoniae </it>patient isolates. In this study, the binding properties of <it>S. pneumoniae </it>isolates and the effects of binding on activation of the Nuclear Factor-Kappa-B (NFκB) pathway and cytokine secretion by type II pneumocytes were measured.</p> <p>Methods</p> <p>Mechanisms of high- and low-binding <it>S. pneumoniae </it>adherence to A549 cells were investigated by blocking putative receptors on bacteria and host cells with antibody and by eluting choline-binding proteins off of bacterial surfaces. NFκB activation was measured by western blot and immunocytochemistry and cytokine secretion was detected by a protein array.</p> <p>Results</p> <p>This study shows that <it>S. pneumoniae </it>isolates from pneumonia patients (n = 298) can vary by as much as 1000-fold in their ability to bind to human lung epithelial cells. This difference resulted in differential activation of the NFκB pathway. High-, but not low-binding <it>S. pneumoniae </it>used Choline-binding protein A (CbpA) to bind to complement component C3 on epithelial cell surfaces. Interleukin-8 (IL-8) was the only cytokine secreted by cells treated with either low- or high-binding <it>S. pneumoniae</it>.</p> <p>Conclusion</p> <p>These results indicate that <it>S. pneumoniae </it>clinical isolates are not homogeneous in their interaction with host epithelial cells. The differential activation of host cells by high- and low-binding <it>S. pneumoniae </it>strains could have implications for the treatment of pneumococcal pneumonia and for vaccine development.</p>