Background
Pertussis: A respiratory tract acute infection with Bordetella pertussis. So many active ingredients exist there in it like pertussis toxin or PTX, FHA, PRN, AGG, etc. Of these, PTX, FHA, PRN and AGG are protective antigenic components, and they have been included in acellular pertussis vaccines.
PTX is one of the most elaborate bacterial protein toxin family members, in the ADP-ribosylating group. It's a polymer protein that has five parts called S1, S2, S3, S4 and S5. PTX is an A-B toxin; the A-protomer with one S1 for ADP-ribosyltransferase and the B-oligomer with S2, S3, S5 and two S4. Since its discovery, PTX has been recognized as playing a crucial role in the pathogenesis of pertussis. The clinical features of pertussis include leukocytosis and histamine sensitization. PTX went by other names including lymphocytosis-promoting factor, histamine-sensitising factor, islet-activating protein and hemagglutinin. We now know that the majority of these biological functions relies on the ADP-ribosyltransferase activity carried by the S1 subunit. The immunomodulatory properties of PTX can also increase host susceptibility to infection. In mouse models, co-infection with PTX-producing strains significantly enhanced the ability of Bordetella parapertussis to infect mice.
Figure 1. Crystal structure of the pertussis toxin
(Source: Coutte L, et al. 2015)
PTX can also trigger both MyD88-dependent and independent signalling in dendritic cells, which in turn drives natural immune responses. On the cellular level, neutrophils are involved in innate immunity, and phagocytose bacteria through antibody- and complement-based receptors called FcR and CR3. PTX slows neutrophil migration and migration into the respiratory tract for the first week after Bordetella pertussis infection, by modulating chemokine receptor signalling in neutrophils. As well as activating protective antibodies, PTX can also increase Th1 and Th2 cell release of cytokines, T-cell proliferation, and the release of IFN-γ and IL-2. It also induces costimulatory molecules CD28 and CD69 expression on T cell surfaces that in turn polyclonally stimulate CD8+ T cells. Furthermore, PTX enhances the recognition and activation signal transmission between T cells and antigen-presenting cells, generating cell-mediated immune responses. PTX also possesses adjuvant properties. When used as an immunological adjuvant, PTX can promote Th17 differentiation through IL-6 induction, which is consistent with studies showing that B. pertussis infection induces a mixed Th1/Th17 immune response.
Alternative Names
Native B. pertussis toxin (Frozen)
Native PTX (Frozen)
Native PT (Frozen)
References
- 1. Coutte L, et al. Investigating pertussis toxin and its impact on vaccination. Future Microbiol. 2015;10(2):241-54.
- 2. Fedele G, et al. T-cell immune responses to Bordetella pertussis infection and vaccination. Pathog Dis. 2015 Oct;73(7):ftv051.