Mechanisms of immune modulation by Fasciola hepatica: Importance for vaccine development and for novel immunotherapeutics

Publisher:
Wiley-VCH Verlag GmbH & Co. KGaA
Publication Type:
Chapter
Citation:
Parasitic Helminths: Targets, Screens, Drugs and Vaccines, 2012, 1, pp. 451 - 463
Issue Date:
2012-01
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The liver fluke Fasciola hepatica can live for long periods in its definitive mammalian host. This longevity is related to the parasite's ability to modulate host immune responses to benefit its survival (i.e., suppression of Th1/Th17 responses and the promotion of strong Th2/Treg-mediated responses). Various reports indicate that this immune regulation may reduce the capacity of animals to resist other bystander infections (e.g., F. hepatica-infected mice exhibit reduced protective immune responses to the respiratory bacterium, Bordetella pertussis). Experiments in cattle infected with F. hepatica revealed reductions in interferon-? responses to coinfections with Mycobacterium bovis. Molecules secreted by the parasite such as cathepsin L cysteine peptidases, the antioxidant peroxiredoxin, and a cathelicidin-like defense molecule play central roles in manipulating the function of host innate immune cells, and thus the development of protective adaptive immune responses. While these molecules influence innate immune cells in distinct ways, they likely function in concert to establish the potent Th2/Treg-mediated immune environment in the host. Vaccines that prevent the action of these immunomodulatory molecules may not only protect animals against liver fluke disease, but reduce their susceptibility to coincident parasitic or microbial infections. Taking a broader view, understanding how the liver fluke influences host immunity via specific cell surface receptors and intracellular signaling pathways could reveal strategies to selectively suppress certain inflammatory processes, and eventually lead to immunotherapeutic treatments for conditions such as arthritis, inflammatory bowel disease, and diabetes
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