Fasciola hepatica primoinfections and reinfections in sheep drive distinct Th1/Th2/Treg immune responses in liver and hepatic lymph node at early and late stages
Autor
Ruiz-Campillo, María Teresa
Barrero‑Torres, Diana María
Abril, Nieves
Pérez, José
Zafra Leva, Rafael
Buffoni Perazzo, Leandro
Martínez Moreno, Álvaro
Martínez-Moreno, Francisco Javier
Molina-Hernández, Verónica
Editor
SpringerFecha
2023Materia
Fasciola hepaticaPrimoinfections
Reinfections
Immune response
Liver
Hepatic lymph nodes
Th1
Th2
Treg
Vaccine
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The expression of proinflammatory (IL-1β, IFN-γ, TNF-α) and regulatory (IL-10, TGF-β, IL-4) cytokines, as well as the
transcription factor FoxP3, was quantified in the liver and hepatic lymph node (HLN) of sheep primoinfected and reinfected
with Fasciola hepatica at early (4, 8 and 16 days post-infection [dpi]) and late (100 dpi) stages. The liver exerted
a Th2 immune response at very early stages after the primoinfection with F. hepatica that induced the downregulation
of IFN-γ, followed by a Th1/Th2/Treg response although the late stages were characterised by the expression of Th1/
Th2 immune mediators. Contrarily, in reinfected sheep a robust mixed Th1/Th2/Treg immune response was found
at very early stages meanwhile at late stages we observed a Th2/Treg immune response overcoming the expression
of Th1 immune mediators. However, the HLN displayed a completely different Th1/Th2/Treg expression profile
compared to the liver. Primoinfections with F. hepatica in HLN induced a mixed Th1/Th2/Treg environment from early
stages, establishing a Th2 immune response at a late stage. However, the reinfected sheep exerted a Th2 immune
response at early stages led by the IL-4 expression in opposition to the Th1/Th2/Treg found in the liver, meanwhile at
late stages the HLN of reinfected sheep exerted a mixed Th1/Th2/Treg immune response. This is the first work publishing
the expression of immune mediators in the liver and HLN from reinfected sheep with F. hepatica. The study of the
immune responses exerted by the natural host in the target organs directly implied in the development of F. hepatica
are crucial to better understand the immunopathogenesis of the fasciolosis being a key factor to develop effective
vaccines.