Defect of protective immunity to Schistosoma mansoni infection in Mongolian gerbils involves limited recruitment of dendritic cells in the vaccinated skin

Abstract

In Mongolian gerbils, Meriones unguiculatus, the attenuated Schistosoma mansoni vaccine, is known to induce marginal or no resistance to a homologous infection. To clarify the base of defective acquisition of the resistance, we have focused on the induction phase of protective immunity to S. mansoni, i.e. cellular responses in the skin and skin-draining lymph nodes (SLN). Percutaneous exposure to normal or ultraviolet (18mJ/cm2)-attenuated cercariae induced comparable increases in SLN leucocyte counts, in contrast to other attenuated schistosome vaccine models in rodents where attenuated parasites induce more notable increases in SLN leucocyte counts than normal ones. Using serial sections, it was demonstrated that greater numbers of attenuated larvae remained for a longer period in the exposed skin than normal ones. Correlated with cellular responses in the SLN, attenuated and normal schistosomes elicited a comparable degree of response of epidermal Langerhans' cells/putative dermal dendritic cells that were visualized by immunohistochemistry using a monoclonal antibody to a gerbil major histocompatibility complex class II molecule (HUSM-M.g.30). It is speculated that in Mongolian gerbils limited recruitment of dendritic cells around attenuated S. mansoni larvae, at least partially, contribute to defective induction of protective immunity by the attenuated vaccine.

Current Status of Vaccines for Schistosomiasis

“…Much of our understanding of the mammalian immune response to schistosomes is based on the use of gene-disrupted (knockout) mice (51,86,125,143,167) and the immunization of mice, nonhuman primates, or other mammalian hosts with UV-or ␥-irradiated cercarial vaccines, with or without a subsequent challenge infection with nonattenuated cercariae (12,41,59,75,76,132,146). The attenuated larvae fail to mature into adult worms and do not produce eggs, so any results obtained are not confounded by egg-induced liver pathology.…”

Gerbils

“…Gerbils have been used to study all aspects of the trematode life cycle including infectivity and immunology as well as to study potential treatments. These trematodes include Schistosoma mansoni, Schistosoma japonicum, Schistosoma haemotobium, Schistosoma magreboweie, Echinostoma caproni, and Opisthorcis viverinni (Adam et al, 1993;Boonmars et al, 2009;Chisty et al, 2002;Mahler et al, 1995;Ogbe, 1983;Sato and Kamiya, 2001). Gerbils are also a good host for the avian schistosome, Austrobilharzia variglandis (Bacha et al, 1982).…”

Sequence Determination of the Heavy-Chain Constant Region in Four Immunoglobulin Classes of Mongolian Gerbils (<i>Meriones unguiculatus</i>)

“…They are currently being used in studies of viral [9], bacterial [7], and parasitic [12] infectious diseases. However, the lack of commercially available gerbil-specific immunological regents has hampered immunopathology studies of those diseases.…”