Infection and Immunity
Infection and Immunity
5 years ago

Dairy heifers naturally exposed to Fasciola hepatica develop a type-2 immune response and concomitant suppression of leukocyte proliferation.

Williams, Hartley, Kadioglu, Graham-Brown, Baylis, Clough
Fasciola hepatica is a parasitic trematode of global importance in livestock. Control strategies reliant on anthelmintics are unsustainable due to the emergence of drug resistance. Vaccines are under development, but efficacy is variable. Evidence from experimental infection suggest vaccine efficacy may be affected by parasite-induced immunomodulation. Little is known about the immune response to F. hepatica following natural exposure. Hence we analysed the immune responses over time in calves naturally exposed to F. hepatica infection.Cohorts of replacement dairy heifer calves (n=42) with no prior exposure to F. hepatica, on three commercial dairy farms, were sampled over the course of a grazing season. Exposure was determined through F. hepatica-specific serum antibody ELISA and fluke egg counts. Concurrent changes in peripheral blood leukocyte sub-populations, lymphocyte proliferation and cytokine responses were measured. Relationships between fluke infection and immune responses were analysed using multivariable linear mixed effect models.All calves from one farm showed evidence of exposure, whilst cohorts from the remaining two farms remained negative over the grazing season. A type-2 immune response was associated with exposure, with increased interleukin (IL)-4 production, IL-5 transcription and eosinophilia. Suppression of parasite-specific PBMC proliferation was evident; while decreased mitogen stimulated IFN-γ production suggested immunomodulation, which was not restricted to parasite-specific responses. Our findings show that the global immune response is modulated towards a non-proliferative type-2 state following natural challenge with F. hepatica This has implications for vaccination programmes in terms of the timing of administration of vaccination programmes, and for host susceptibility to co-infecting pathogens.

Publisher URL: http://doi.org/10.1128/IAI.00607-17

DOI: 10.1128/IAI.00607-17

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