Schistosoma mansoni: larval damage and role of effector cell(s) in the synergy between vaccine immunity and Praziquantel treatment

Abstract

A number of authors have demonstrated that the schistosomicidal compound, Praziquantel (Pzq), depends for its action upon the immune status of the host (Sabah et al. 1985; Brindley & Sher, 1987; Doenhoff et al. 1987). We have attempted to define the synergistic interaction between immuno- and chemotherapy further, using the murine irradiated vaccine model of schistosomiasis mansoni. In vaccinated mice, resistance operates in the skin but not the lungs; drug targeted towards lung-stage worms exacerbates lung-phase immunity, however, as depicted by the increased number and size of inflammatory reactions in the pulmonary tissues. Parasites are often found trapped within such foci. In the present investigation, light and ultrastructural studies have been utilized to examine the nature and extent of damage inflicted upon lung-stage larvae recovered from day 6 Pzq-treated vaccinated mice. Such studies have revealed that damage involves muscle disorganization, internal disruption and occasionally, loss of the tegument; in the latter case, cells are often seen attached to the denuded lung worms. To identify the crucial cellular effector cell(s) involved in the synergy between immuno- and chemotherapy, cell depletion studies have been performed in vivo. It would appear from these experiments that eosinophils or lymphocytes rather than neutrophils or macrophages are important effector cells in this synergy. Histological studies argue in favour of eosinophils being the key effector cells.

Paramyosin is a major target of the human IgA response against Schistosoma japonicum

“…Combined with previous observations of pulmonary eosinophilia in mice multiply immunized with irradiated cercariae and treated with praziquantel (Menson et al . 1989, Piper et al . 1991), and the fact that IL‐5, a central regulator of eosinophil biology and promoter of IgA biosynthesis, are elevated among resistant individuals (Roberts et al .…”

Active immunization of mice with Schistosoma mansoni worm membrane antigens enhances efficacy of praziquantel

“…Alternatively, Mehlhorn and others (1981) have described the adherence of granulocytes to PZQ-treated worms one hour after drug treatment, which may indicate a role for cells in the elimination of drug 'damaged' worms in an ADCC-like reaction. Cellular activity against PZQtreated parasites has been particularly well documented with respect to treatment of lung schistosomula in vaccinated mice, with eosinophil being the major effector cells (Piper et al 1991). Further studies are, however, required to determine more exactly the mechanisms by which host immunity and drugs synergize in the killing of schistosomes.…”

Chemotherapy and immunity in opportunistic parasitic infections in AIDS

“…The relationship between chemotherapy and immunity in experimental parasitic infections is increasingly being denned (Brindley & Sher, 1987Doenhoeff et al 1991;Iwobi, Doenhoff & Neal, 1991;Piper et al 1991). However, evidence pointing to the interaction between chemotherapy and immunity in parasitic infections in AIDS patients is only indirect, arising from the clinical observations that reactivation and relapse of these infections, despite appropriate chemotherapy, correlates with decline in cell-mediated immunity.…”