Recent studies revealed that Th17 cells increase the clearance of B. Butylhydroxyanisole pertussis after an intranasal infection in animals. Infection with B. pertussis induces also B-cell and antibody mediated immunity. Microarray analysis showed increased gene expression of the BCR in the lungs. In addition, gene expression of IgM, IgG and IgA was observed in lungs and spleen. Whereas, most genes for antibody isotypes were found up-regulated in both tissues, IgM was down-regulated in the spleen. This was confirmed by the detection of IgA and IgG after 14 days p.i. However, IgM antibodies were not found systemically. In mice, IgG1 is associated with a Th2-like response, while IgG2a and IgG2b suggest induction of a Th1 response. IgG2b is also linked to Th17 lymphocytes. All antibody responses in the present study were directed against whole cell B. pertussis and outer membrane vesicles, but not against the B. pertussis antigens that are typically present in acellular vaccines: Ptx, Prn, FHA and Fim2/3. However, memory Th1/Th17 cells were detected upon re-stimulation with Prn and FHA. The polymeric immunoglobulin receptor was highly expressed during the whole course of B. pertussis infection in the lungs. pIgR is essential for the transport of IgA into the mucus and is seen as a bridge between innate and adaptive mucosal responses. The expression of pIgR was drastically enhanced 14 days p.i., leading to secretion of mucosal IgA in the lungs. Interestingly, the increased pIgR expression coincided with IL17A production in the lungs and sera, which is in agreement with the finding that Th17-mediated responses influence the local humoral response by inducing pIgR expression and elevating secretory IgA levels. Therefore, the transport of IgA to the mucosa, which is orchestrated by IL-17A via the induction of pIgR, supports an important role for local immunity. In summary, B. pertussis infection induces a broad humoral response, which was observed by gene and protein expression. After the lungs and the draining lymph nodes, the spleen is the third organ in line involved in the generation of the immune response. Therefore, gene expression effects could be less abundant. Furthermore, the spleen consists of many cell types with different gene expression profiles, so changes in expression levels in a single cell type might not have been detected. Cell sorting of individual cell types and subsequent gene expression profiling could overcome this problem. Second, specific antibody and T-cell responses were only measured for a limited set of available purified antigens. The inclusion of other antigens, such as outer membrane proteins, would perhaps have allowed a more detailed analysis. Third, in this study we propose murine infectioninduced immune signatures as a benchmark to be used in the development of improved human pertussis vaccines. Since B. pertussis is not a natural pathogen for mice, translation of the results obtained in this study to the human situation remains to be interpreted with caution. Nodakenin Nevertheless, using a murine model has several advantages. It is regarded an important small animal model for pertussis vaccine development and enables to dissect the local and systemic immune response in great detail, as shown in this study, rather than using blood or nasal washes from humans undergoing a B. pertussis infection. Furthermore, the role of individual gene signatures and products could be assessed in future research in mice by using knockin or knockout strains, or by functional interventions.
Th17 cells have been indicated as key cells to control bacterial infections at mucosal sites
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