Immunity and immune modulation elicited by the larval cestode Mesocestoides vogae and its products

Abstract

Larval cestodes (metacestodes) induce long-lasting infections leading to considerable pathology in humans and livestock. Their survival is typically associated with Th2-biased immune responses and immunosuppressive effects and depends on the parasite's ability to excrete/secrete antigens with immunoregulatory properties. Here, Mesocestoides vogae, a natural parasite of mice, is proposed as a new model species for the identification and characterization of cestode-derived immunomodulatory factors. We followed the kinetics of immune parameters after infection with M. vogae or exposure to their excretory/secretory (ES) products in a permissive strain of mice. Besides, a dominant IL-10 production and accumulation of macrophages and eosinophils expressing mRNA for Fizz-1, YM1 and Arg-1, mice showed minimal IFN-γ and transient IL-4 production at early time points with a complete loss at later stages of infection. We found that serum-free ES products without host contamination directly induced M2 macrophages and suppressed IFN-γ production in vivo and in vitro. This study highlights the use of the M. vogae as a cestode infection model and its ES products as a valuable tool for the identification of new therapeutic targets for the control of larval cestodiasis.

In vitro culture of Mesocestoides corti metacestodes and isolation of immunomodulatory excretory–secretory products

“…As in the case of helminth infections, M. corti tetrathyridia mediate a chronic disease that is associated with parasite‐induced T helper‐2 (Th2) and tolerogenic immune responses . Research on nematode and trematode systems has demonstrated the importance of DCs in the induction of such immunosuppressive mechanisms .…”

“…Dendritic cells (DCs) exert major functions not only to elicit immune responses but also to regulate immune tolerance. Therefore, DCs are major targets for microbial immune evasion by specifically blocking their IL‐12 production to deviate the immune response to type‐2 immune response as observed for all groups of helminths such as trematodes , nematodes and as shown by us more recently also for cestodes .…”

“…The ability to multiply in laboratory mice encouraged studies on M. corti as a model for larval cestode infections . Like clinically relevant cestodes , M. corti alters the host immune response and releases ES products , likely facilitating the colonization of immunocompetent mice. Voge and Coulombe (1966) demonstrated the ease of in vitro cultivation of M. corti tetrathyridia achieving larval multiplication at a rate comparable to that observed in the mouse model .…”

Cellular And Humoral Peritoneal Immunity To Mesocestoides Vogae Metacestodes Infection In Mice.

“…In the subsequent experiments aimed at studying the direct effect of parasitic ES antigens, groups of mice (n=5) received either intraperitoneal injections of 200 µl of PBS (control) or 20 µg of ES in 200 µl of PBS and the applications of ES and PBS were performed six times, every day for a total of 6 days. The antigen doses correlated approximately with the concentration of M. vogae secretion detected in vivo [4]. In these experiments, peritoneal uid and PEC were isolated as described below and used in further analysis.…”

“…Invasion of the hepatic tissue by larvae results in extensive parenchymal destruction with brosis and the development of ascites. To date, the experimental model of larval cestodiasis has been preferentially used to study host-parasite interactions, speci cally in the liver [3] or the peritoneum [4]. Intracranial inoculation of metacestodes serves as a laboratory model of neurocysticercosis to study immunity and metacestodes-associated pathology in the brain [5,6].…”