ABSTRACT
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 o f the infectious agent. In particular, these immunomodulating virulence factors may specifically stimulate a T helper type 1 (Thl), a T helper type 2 (ТҺ2) or a mixed Th 1 /ТҺ2 response. Cholera toxin (CT) , Escherichia coli heat-labile toxin (LT) and Bordetallapertussis filamentous haemagglutinin (FHA) usually favour a ТҺ2 immune response. In contrast, Helicobacter pylon neutrophil-activating protein (HP-NAP) andlisteriolysin O (LLO) of Listeria monocytogenes direct the immune response towards a polarised Thl and cell-mediated immune response. Moreover, other virulence factors, such as Bordetella pertussis toxin (PT), ad enylate cyclase toxin (CyaA) and Clostridium difficile toxin A, elicit a mixed ТҺ1/ТҺ2 response with some ability to shift the response between Thl and ТҺ2 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, cer tain Thl-directing or Th2-suppressing immunomodulators have potential applications in cancer therapy, allergic conditions and viral infections where a Thl response is preferable. On the other hand, Th2-driving or Thl-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 o f these immunomodulators are promising candidates as vaccine adjuvants when given with heterologous antigens where they can potentiate an appropriate immune response.
