Resistance to liver fluke infection in the natural sheep host is correlated with a type‐1 cytokine response

Abstract

Indonesian thin-tail (ITT) sheep can resist infection with Fasciola gigantica but not F. hepatica and presents an ideal model to investigate the mechanisms of liver fluke resistance in a natural host. This study examines the local and systemic immune responses of sheep during Fasciola infection and demonstrates that different anatomical tissues display distinct cytokine profiles consistent with liver fluke migration. The study also reveals a significant difference in the cytokine and antibody profiles of ITT sheep infected with F. gigantica compared with F. hepatica, with a higher ratio of IL-4/IFN-γ mRNA expression and specific IgG1/IgG2 antibodies strongly correlating with pathology. Interestingly, the significant type-1 cytokine profile occurred in the lymph node closest to the site of infection at a time when the effective immune response against F. gigantica liver flukes is thought to occur. When the same F. gigantica infection in the resistant ITT sheep was compared with the susceptible Merino breed, the resistant type-1 phenotype against liver fluke infection was only observed in the ITT sheep. These studies provide the first evidence to suggest that the induction of an early type-1 immune response in this natural sheep host may be responsible for the ability to resist liver fluke infection.

Liver fluke vaccines in ruminants: strategies, progress and future opportunities

“…273 Overall, these results suggest that Type 1 immune responses are (Piedrafita et al, 2004;Flynn et al, 2010). In 279 ITT sheep, only local draining lymph nodes showed such a Type 280 1 immune response early after infection but Type 2 responses were 281 induced later in the infection (Pleasance et al, 2011b). This is con-282 sistent with the proposal that Type 2 responses support fluke sur-283 vival .…”

“…in vitro mediated by antibody but the specific types of antibodies involved have not been defined (Piedrafita et al, 2001(Piedrafita et al, , 2007. Ruminant antibody isotypes such as IgG1, IgG2 and IgE may be involved in mediating antibody-dependent cell cytotoxicity (Piedrafita et al, 2007;Pleasance et al, 2011b). T0 bodies (yellow circles), T1 bodies (white circles) and T2 bodies (blue triangles) are shown which are proposed to deliver proteins to the tegument and surface glycocalyx (Hanna, 1980a).…”

A mucin-like peptide from Fasciola hepatica instructs dendritic cells with parasite specific Th1-polarizing activity

“…To date, vaccination trials with either purified native or recombinant F. hepatica proteins have reported a wide range of protection (30–89%) in ruminants151617. Interestingly, it has been proposed that induction of a robust Th1 response could protect the host not only from the infection1518 but also from bystander co-infections by down-regulating Th2 regulatory immunity19. Accordingly, protection induced by helminth vaccines has been associated with high IFN-γ and TNF production20.…”

Inmunidad Celular en Ganado Vacuno Lechero Naturalmente Infectado con Fasciola hepatica en Cajamarca, Perú

“…No obstante, en un estudio en ovejas cola delgada de Indonesia (ITT) resistentes a infección por F. gigantica (Pleasance et al, 2011) y en otro en conejos con alta protección conferidos con una vacuna contra F. hepatica (Espino y Rivera, 2010), se demuestra que una respuesta temprana tipo Th1 o la dominancia de esta está asociada a la protección y resistencia a la infección.…”