Attack and Counter‑Attack: Targeted Immunomodulation Using Bacterial Virulence Factors
Mohammed Bahey-El-Din, Brendan T. Griffin and Cormac G.M. Gahan
Virulence factors of pathogenic bacteria by definition play a crucial role in infectivity and pathogenesis. Many of these factors have evolved to modulate the host immune response often in a manner that favours survival of the infectious agent. In particular, these immunomodulating virulence factors may specifically stimulate a T helper type 1 (Th1), a T helper type 2 (Th2) or a mixed Th1/Th2 response. Cholera toxin (CT), Escherichia coli heat‑labile toxin (LT) and Bordetallapertussis filamentous haemagglutinin (FHA) usually favour a Th2 immune response. In contrast, Helicobacter pylori neutrophil‑activating protein (HP‑NAP) and listeriolysin O (LLO) of Listeria monocytogenes direct the immune response towards a polarised Th1 and cell‑mediated immune response. Moreover, other virulence factors, such as Bordetella pertussis toxin (PT), adenylate cyclase toxin (CyaA) and Clostridium difficile toxin A, elicit a mixed Th1/Th2 response with some ability to shift the response between Th1 and Th2 depending upon the context. These immunomodulating properties suggest a potential use for these virulence factors, in a detoxified or modified form, to deliberately direct the immune response towards a desired state. Thus, certain Th1‑directing or Th2‑suppressing immunomodulators have potential applications in cancer therapy, allergic conditions and viral infections where a Th1 response is preferable. On the other hand, Th2‑driving or Th1‑suppressing immunomodulators may be used in conditions where the pathology is mainly due to an exaggerated inflammatory response as is the case in Crohn’s disease. Moreover, all of these immunomodulators are promising candidates as vaccine adjuvants when given with heterologous antigens where they can potentiate an appropriate immune response.