Abomasal dysfunction and cellular and mucin changes during infection of sheep with larval or adult Teladorsagia circumcincta

Abstract

This is the first integrated study of the effects on gastric secretion, inflammation and fundic mucins after infection with L3 T. circumcincta and in the very early period following transplantation of adult worms. At 3 months-of-age, 20 Coopworth lambs were infected intraruminally with 35,000 L3; infected animals were killed on Days 5, 10, 15, 20 and 30 post-infection and 6 controls on either Day 0 or 30 post-infection. Another 15 Romney cross lambs received 10,000 adult worms at 4–5 months-of-age though surgically-implanted abomasal cannulae and were killed after 6, 12, 24 and 72 hours; uninfected controls were also killed at 72 hours. Blood was collected at regular intervals from all animals for measurement of serum gastrin and pepsinogen and abomasal fluid for pH measurement from cannulated sheep. Tissues collected at necropsy were fixed in Bouin’s fluid for light microscopy, immunocytochemistry and mucin staining and in Karnovsky's fluid for electron microscopy. Nodules around glands containing developing larvae were seen on Day 5 p.i., but generalised effects on secretion occurred only after parasite emergence and within hours after transplantation of adult worms. After L3 infection, there were maximum worm burdens on Days 10–15 post-infection, together with peak tissue eosinophilia, inhibition of gastric acid secretion, hypergastrinaemia, hyperpepsinogenaemia, loss of parietal cells, enlarged gastric pits containing less mucin and increased numbers of mucous neck cells. After adult transplantation, serum pepsinogen was significantly increased after 9 hours and serum gastrin after 18 hours. Parallel changes in host tissues and the numbers of parasites in the abomasal lumen suggest that luminal parasites, but not those in the tissues, are key drivers of the pathophysiology and inflammatory response in animals exposed to parasites for the first time. These results are consistent with initiation of the host response by parasite chemicals diffusing across the surface epithelium, possibly aided by components of ES products which increased permeability. Parietal cells appear to be a key target, resulting in secondary increases in serum gastrin, pit elongation, loss of surface mucins and inhibition of chief cell maturation. Inflammation occurs in parallel, and could either cause the pathology or exacerbate the direct effects of ES products.

Local and systemic immune mediators of Morada Nova lambs with divergent Haemonchus contortus resistance phenotypes

“…Eosinophils and mast cells are the main cellular populations involved in defence against helminths, including H. contortus 20,21 . GIN infection is known to induce eosinophilia and mastocytosis in the sheep gastrointestinal tract 21,23,24 . Enhanced resistance against H. contortus and T. circumcincta is frequently associated with higher numbers of eosinophils and mast cells in the abomasal mucosa, in comparison with susceptible sheep, which have a delayed and less intense response 22,42,43 .…”

“…Th2‐polarized response triggers IgE synthesis and an increase in local eosinophils and mast cells, which release proteins responsible for helminth clearance, especially against larval forms, through specific IgE recognition by high affinity receptors (FcεRI) in an “antibody‐mediated cytotoxicity” 20,21 . Sheep with increased resistance to H. contortus have been characterized by pronounced local or systemic eosinophilia and local mastocytosis 13,22‐24 . Superior expression of the FcεRI‐encoding gene ( MS4A2 ) has also been observed in resistant sheep 12,15 …”

“…20,21 Sheep with increased resistance to H. contortus have been characterized by pronounced local or systemic eosinophilia and local mastocytosis. 13,[22][23][24] Superior expression of the FcεRI-encoding gene (MS4A2) has also been observed in resistant sheep. 12,15 Regarding humoral responses, high IgG and IgA levels in the mucosal barriers are associated with GIN defence, wherein increased local and systemic levels of these antibodies have been found in GIN-resistant sheep.…”

“…Regarding the local response, higher IgA levels were observed in the abomasal mucus of the resistant lambs, indicating a direct role for this isotype in parasite resistance.Eosinophils and mast cells are the main cellular populations involved in defence against helminths, including H. contortus 20,21,23,24. Enhanced resistance against H. contortus and T. circumcincta is frequently associated with higher numbers of eosinophils and mast cells in the abomasal mucosa, in comparison with susceptible sheep, which have a delayed and less…”

Implication of the fecal egg count reduction test (FECRT) in sheep for better use of available drugs

“…The main health issue affecting sheep around the world is gastrointestinal nematode infection (CHARLIER et al, 2014). Production rates drop due to parasitic spoliation (SCOTT et al, 2017), reduced voluntary food intake (VALDERRÁBANO et al, 2002) and efficiency of food utilization (BLACKBURN et al, 2015), and due to the mobilization of immune system cells to fight parasitism (HOSTE et al, 2005). In the attempt to control these diseases, anthelmintics (AH) have been used indiscriminately, causing them to gradually lose their effectiveness (KAPLAN & VIDYASHANKAR, 2012).…”