Fasciola hepatica Suppresses a Protective Th1 Response against Bordetella pertussis

ABSTRACT Fasciolosis, like other helminth infections, is associated with the induction of T-cell responses polarized to the Th2 subtype. Respiratory infection with Bordetella pertussis or immunization with a pertussis whole-cell vaccine (Pw) induces a potent Th1 response, which confers a high level of protection against bacterial challenge. We have used these two pathogens to examine bystander cross-regulation of Th1 and Th2 cells in vivo and provide evidence of immunomodulation of host T-cell responses to B. pertussis by a concomitant infection with Fasciola hepatica. Mice with a coinfection of F. hepatica and B. pertussis exhibited a Th2 cytokine profile in response to F. hepatica antigens, similar to those infected with F. hepatica alone. By contrast, the Th1 response to B. pertussis antigens was markedly suppressed and the bacterial infection was exacerbated following infection withF. hepatica. Furthermore, an established Th1 response induced in mice by infection with B. pertussis or by parenteral immunization with Pw was also suppressed following infection with F. hepatica. This immunomodulatory effect of B. pertussis-induced responses by F. hepatica infection is significantly reduced, but not completely abrogated, in IL-4 knockout mice. Our findings demonstrate that Th2-inducing parasites can exert bystander suppression of protective Th1 responses to infection or vaccination with a bacterial pathogen and that the modulation is mediated in part by IL-4 and, significantly, is effective at both the induction and effector stages of the Th1 response.