Regulation of macrophage-mediated larvicidal activity inEchinococcus granulosusandMesocestoides corti(Cestoda) infection in mice

Abstract

Killing of metacestodes by normal or post-infection macrophages and the regulation of this activity by cytokines were studied in vitro. The protoscolecidal activity of normal macrophages against Echinococcus granulosus was inhibited by a product of naive T-enriched lymphocytes co-cultured with protoscoleces (PSC). By contrast, supernates from co-cultures of Mesocestoides corti tetrathyridia (MCT) and T-enriched or B-enriched normal lymphocytes increased killing of MCT by normal macrophages. Larvicidal activity (against both PSC and MCT) was enhanced by high concentrations of macrophage-activating factors produced by Con A-stimulated rat lymphocytes (Con A-LK), but was reduced by low concentrations of these factors. Activation by synergism between Con A-LK and recombinant interferon-gamma(r. IFN-gamma) was demonstrated in macrophage-mediated killing of MCT at high effector to target ratio. Cytokine-activation of normal or post-MCT infection macrophages was compared. Macrophages from both 8 and 20 week post-infection mice were refractory to lymphokines from lymphocyte-MCT cultures and displayed greatly reduced killing of MCT. Macrophage activation by Con A-LK and r.IFN-gamma was also impaired, implying a general defect in the ability of these post-infection macrophages to respond to macrophage activating signals. The data indicate that two different mechanisms may exist by which metacestodes regulate potentially larvicidal effector mechanisms. E. granulosus can elicit the production of lymphokines suppressive for PSC killing, whereas M. corti appears directly to induce a refractory state in effector macrophages.

Cytokine response and outcome of infection depends on the infective dose of parasites in experimental infection by Echinococcus granulosus

“…It is interesting to observe that the establishment of infection was low in 43% of the individuals from the group infected with the low dose compared to the group infected with the high dose. Macrophages are pivotal cells in the immune system because of their effector and regulatory activities (16,28), and they have been proposed as effector cells against different parasites provided they are activated by IFN‐γ (15,16,29,30). Our in vitro experiments indicate that IFN‐γ‐activated adherent PEC can kill protoscoleces, probably through the release of nitric oxide.…”

Concepts in Immunology and Diagnosis of Hydatid Disease

“…The majority of parasite killing occurs within the first 2 weeks postinfection. Activated macrophages are involved in the killing of Echinococcus PSC (8,9,24,142). Studies in vitro indicate that macrophage-dependent killing of PSC can be increased by IFN-␥ (148) and decreased by some cytokines such as IL-10 or IL-4 (142).…”

Effects of free and liposomized praziquantel on the surface morphology and motility of Mesocestoides vogae tetrathyridia (syn. M. corti ; Cestoda: Cyclophyllidea) in vitro

“…Although the host's immune system responds to M. corti (syn. vogae) infections by several mechanisms (Mitchell and Handman 1977;Jenkins et al 1990), spontaneous removal of the infection has never been observed.…”