Bordetella pertussis toxin induces the release of inflammatory cytokines and dendritic cell activation in whole blood: impaired responses in human newborns

Pertussis Toxin Reduces the Number of Splenic Foxp3+ Regulatory T Cells

“…This 105-kDa protein complex is produced by Bordetella pertussis, the bacterium responsible for whooping cough in humans. PTx is immunogenic and involved in the pathogenesis of B. pertussis infection (7,8) and, therefore, has been included in some acellular pertussis vaccines in a chemically or genetically detoxified form (9).…”

Pertussis toxin as an adjuvant suppresses the number and function of CD4+CD25+ T regulatory cells

“…To date, the cellular target and action mechanism by which PTx mediates adjuvanticity remains to be defined [21]. Over the past few years, it has been reported that PTx promoted the activation and maturation of APC, especially dendritic cells [17][18][19][20][21], and a recent report suggests this may be based on the activation of TLR4 by PTx [16]. However, these findings were based on in vitro observations, and the mechanism of in vivo action of PTx remains largely obscure.…”

“…PTx treatment inactivates chemokine receptors and results in the redistribution of lymphocytes [31], manifested by inhibition of entrance of lymphocytes into LN and Peyer's patches and by accumulation of cells in the spleen [32]. Our data show that the ADP-ribosyltransferase activity of PTx is required for the reduction of Treg activity, whereas ADP-ribosyltransferase activity was reported to be unnecessary for PTx to stimulate immune responses (the activation of APC and production of cytokines) [18]. Therefore, inactivation of PTx-sensitive G-proteincoupled receptors and alteration of leukocyte trafficking could be critical for the reduction in Treg cells.…”

“…Recent work has shown that PTx actually increases adhesion molecule expression that initiates leukocyte infiltration into the brain [16]. Further, PTx appears to induce the maturation of dendritic cells [17][18][19][20][21], which results in the expansion of T effector cells and secretion of IFN-c [22].…”

Perinatal Activation of the Interleukin-33 Pathway Promotes Type 2 Immunity in the Developing Lung

“…IL-12p35 is the rate limiting subunit of IL-12p70, the predominant cytokine driving Th1 cell development. These data are in line with previous work showing that human cord blood DCs (De Wit et al, 2003;Goriely et al, 2001;Tonon et al, 2002) and mouse splenic DCs (Lee et al, 2008) are deficient in IL-12 production. In neonatal lung DCs, IL-12p35 deficiency was strongest in CD11b + cDCs and CD64 + moDCs, the two main HDM-presenting DC subsets.…”