Neutrophil numbers is matched by a corresponding steady decrease in bacterial CFUs

The 24�C48 hour peak of neutrophil influx coincides with a significant drop in bacterial load in the lung and the subsequent decline in lung. This pattern of rapid neutrophil influx and gradual decline is in keeping with other respiratory pathogen Taltirelin infection models of the lungs e.g. streptococcus pneumonia, where early and rapid neutrophil influx is ineffectual in clearance and containment of bacterial loads. In contrast, B cell and T cellinflux into the lung progressively increased over the study period of 7 days postinfection. To our knowledge no previous studies have documented B cell recruitment into the lung following P aeruginosa infection. In contrast, T cell responses have been studied with CD4 cell Th2 and Th17 type responses being described in human P. aeruginosa infection, while CD4 Th1 cells have been reported to be protective in mice. In order to understand better how the observed recruitment of B and T cells into the lungs is mediated, we looked at expression of the homeostatic chemokines, CXCL13, CCL19 and CCL21, known to influence lymphocyte migration and to be expressed by epithelial, endothelial and dendritic cells. Increased CXCL13 expression from day 1 post infection preceded increased CCL19 and CCL21. Elevation of CXCL13, primarily a B cell chemoattractant with highest expression on days 1 and 2 coincided with the increase in B cell numbers, suggesting that this chemoattractant may be important in the local B cell response to P. aeruginosa, possibly Clofentezine supporting the recruitment of both B1 and B2 B cell types. In contrast, expression of the B cell, T cell and DC chemoattractants CCL19 and CCL21 increased progressively to 7 days post infection with CCL19 elevated at day 1 and rising before CCL21. A previous study, using the PAO1 strain, reported increased expression of CCL19 but not CCL21 on day 1 following P. aeruginosa infection but did not study later time points. The data presented here show that both are upregulated post infection but with differential kinetics, CCL19 levels initially being increased before CCL21, although CCL21 is expressed at higher levels by day 7. Our data supports a role for these two chemokines in later recruitment of B and T lymphocytes and potentially DCs whilst CCL19 could also have a role in the early recruitment of B cells. CXCL13, CCL19 and CCL21 have previously been shown to be essential components of the local airway immune response to viral infectionand to be involved in iBALT formation, a recognised feature of long term pathogen exposure. It is possible that recruitment of both B and T cells seen in this study represents the early stages of iBALT formation and the induction of a local adaptive immune response. Our results demonstrate that increased BAFF expression is a characteristic of the airway immune response at similar time points to increased expression of B cell chemoattractant and elevated B cell numbers. This suggests that not only are B cells recruited to the airway but that the local environment is capable of supporting B cell survival, differentiation and antibody production. Colorectal canceris still a leading cause of cancer-related morbidity and mortality around the world, although a lot of progress has been made in the treatment of CRC over the past years.

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