Cytokine, Antibody and Proliferative Cellular Responses Elicited by Taenia solium Calreticulin upon Experimental Infection in Hamsters

Abstract

Taenia solium causes two diseases in humans, cysticercosis and taeniosis. Tapeworm carriers are the main risk factor for neurocysticercosis. Limited information is available about the immune response elicited by the adult parasite, particularly the induction of Th2 responses, frequently associated to helminth infections. Calreticulin is a ubiquitous, multifunctional protein involved in cellular calcium homeostasis, which has been suggested to play a role in the regulation of immune responses. In this work, we assessed the effect of recombinant T. solium calreticulin (rTsCRT) on the cytokine, humoral and cellular responses upon experimental infection in Syrian Golden hamsters (Mesocricetus auratus). Animals were infected with T. solium cysticerci and euthanized at different times after infection. Specific serum antibodies, proliferative responses in mesenteric lymph nodes and spleen cells, as well as cytokines messenger RNA (mRNA) were analyzed. The results showed that one third of the infected animals elicited anti-rTsCRT IgG antibodies. Interestingly, mesenteric lymph node (MLN) cells from either infected or non-infected animals did not proliferate upon in vitro stimulation with rTsCRT. Additionally, stimulation with a tapeworm crude extract resulted in increased expression of IL-4 and IL-5 mRNA. Upon stimulation, rTsCRT increased the expression levels of IL-10 in spleen and MLN cells from uninfected and infected hamsters. The results showed that rTsCRT favors a Th2-biased immune response characterized by the induction of IL-10 in mucosal and systemic lymphoid organs. Here we provide the first data on the cytokine, antibody and cellular responses to rTsCRT upon in vitro stimulation during taeniasis.

Orally administered Taenia solium Calreticulin prevents experimental intestinal inflammation and is associated with a type 2 immune response

“…We previously showed that oral administration of rTsCRT induced a predominantly type 2 response that conferred partial protection against T . solium taeniasis and was able to stimulate the expression of regulatory cytokines during taeniosis in an experimental hamster model [ 21 , 23 ]. In addition, rTsCRT mainly induced the type 2 cytokines IL-4 and IL-5 as well as specific anti-rTsCRT IgG1, as a result of oral immunization in mice [ 24 ].…”

“…polygyrus , Necator americanus and T . solium [ 20 , 21 , 23 , 24 , 51 ] have Th2 skewing potential in contrast to human and mouse calreticulins, which induce pro-inflammatory cytokines [ 52 , 53 ]. Whether the ability of calreticulin to promote type 2 responses is a conserved property only of helminth parasites is an interesting issue and warrants additional research.…”

“…We have previously described the ability of orally administered recombinant Taenia solium calreticulin (rTsCRT) as a candidate vaccine to reduce worm burden in a hamster model of taeniosis by inducing a IL-4 and hyperplasia of goblet cells in the small intestine and to reduce the DNA damage brought about by the presence of the tapeworms [ 21 , 22 ]. rTsCRT was also able to induce production of IL-4 and IL-10 when incubated in vitro with mesenteric lymph node and spleen cells [ 23 ]. Therefore, we hypothesized that oral immunization with rTsCRT might promote an immunomodulatory environment that prevents the development of colitis using the model of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced acute colonic inflammation.…”

Recent advancements and new perspectives in animal models for Neurocysticercosis immunopathogenesis

“…When infected with eggs, they also reported that copro‐antigen ELISA was positive up to 18 weeks post‐infection in infected animals. Recently, Mendlovic et al., (2015) used this model to study the cytokines and proliferative cellular response after recombinant T. solium calreticulin (rTsCRT) infection in hamsters having T. solium taeniosis. They found dominant Th2 immune response with significantly high IL‐10 and IL‐4 cytokines.…”

“…Several animal models such as mice, rats, pigs, gerbils, rabbits, cats, monkeys and dogs have been tried for cysticercosis, but cysticercosis T A B L E 1 Some major taeniid species and their intermediate host animals that have been used in animal model studies with their references Pig ( 12-24 ), Hamster,[25][26][27][28] Chinchilla,29 Rat,30 Monkey 31…”