Via murine infection models of B. pertussis (Bp) and Bp{Delta}PTX (Bp strain devoid of pertussis toxin [PTX]), we tested the hypothesis that PTX inhibits the expression of G-protein coupled receptors (GPCR) on dendritic cells (DC) and of mucosal-associated trafficking receptors (MATR) on CD4+ effector memory T cells. Lung plasmacytoid DC (pDC) increased during early infection with both strains. However, a reduced percentage of pDC from Bp infected lung expressed co-stimulatory molecules and the GPCR required for migration to secondary lymph nodes. Additionally, a modest rise of circulating Th1 cells was observed during early Bordetella infections. However, in Bp infection, a reduced number expressed MATR compared to those from Bp{Delta}PTX infection. Interestingly, at 10-25 days post infection, blood Th17 cells rose dramatically, followed by accumulation in the lung and a gradually elevated display of MATR. Lung T-regulatory cells arose in tandem with increased lung Th17 level, perhaps controlling the rise in lung inflammation. The temporal correlation between pDC and memory responses suggests that pDC responses, driven perhaps by opsonized Bordetella antigens, may interfere with the imprinting of MATR on CD4+ effector memory T cells. We conclude that the PTX-dependent defective MATR imprinting on Th1 cells and delayed polarization into Th17 cells expressing MATR during Bp infection in mice may be responsible for the prolonged disease and suggest a role of pDC in this mechanism.