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

Cestode-mediated diseases hold the interesting feature of persisting metacestode larvae dwelling within the host tissues, in the midst of the immune response. Excretory-secretory (ES) products of the metacestode larval stage modulate the host immune response and modify the outcome of the disease. Therefore, isolation and analysis of axenic metacestode ES products are crucial to study their properties. Here, we report the development of a system for long-term in vitro cultivation of the metacestode of the parasitic cestode Mesocestoides corti (syn. Mesocestoides vogae). Although feeder cells and host serum supported the early growth of the parasite, long-term survival was not dependent on host serum or host-derived factors enabling the collection of parasite released products in serum-free medium. Functionally, these axenic ES products recapitulated M. corti tetrathyridia's ability to inhibit LPS-driven IL-12p70 secretion by dendritic cells. Thus, our new axenic culture system will simplify the identification and characterization of M. corti-derived immunomodulatory factors that will indirectly enable the identification and characterization of corresponding factors in the metacestode larvae of medically relevant cestodes such as Echinococcus multilocularis that are not yet amenable to serum-free cultivation.

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

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.