Agranulocytosis leads to intestinalEchinococcus multilocularisoncosphere invasion and hepatic metacestode development in naturally resistant Wistar rats

Abstract

Susceptibility to Echinococcus multilocularis infection considerably varies among intermediate (mostly rodents) and dead-end host species (e.g. humans and pig), in particular regarding intestinal oncosphere invasion and subsequent hepatic metacestode development. Wistar rats are highly resistant to infection and subsequent diseases upon oral inoculation with E. multilocularis eggs, however, after immunosuppressive treatment with dexamethasone, rats become susceptible. To address the role of the cellular innate immunity, Wistar rats were individually or combined depleted of natural killer (NK) cells, macrophages (MΦ) and granulocytes (polymorphonuclear cells, PMN) prior to E. multilocularis egg inoculation. Although NK cell and MΦ depletion did not alter the resistance status of rats, the majority of PMN-depleted animals developed liver metacestodes within 10 weeks, indicating that PMN are key players in preventing oncosphere migration and/or development in Wistar rats. In vitro studies indicated that resistance is not caused by neutrophil reactive oxygen species or NETosis. Also, light microscopical examinations of the small intestine showed that oral inoculation of E. multilocularis eggs does not elicit a mucosal neutrophil response, suggesting that the interaction of oncospheres and neutrophils may occur after the former have entered the peripheral blood. We suggest to consider granulocytes as mediators of resistance in more resistant species, such as humans.

Early-phase migration dynamics of Echinococcus multilocularis in two mouse strains showing different infection susceptibilities

“…Administration of immunosuppressive drug (Armua-Fenandez et al, 2016;Joekel and Deplazes, 2017) and depletion of granulocytes (Joekel et al, 2020) resulted in the parasite establishment in the liver of Wistar rats, which are completely resistant to E. multilocularis infection, suggesting that innate immunity has critical roles for infection defence. In the study by Joekel et al (2020), the authors concluded that the interaction of oncospheres with granulocytes may take place only in blood stream since any pathological changes or neutrophil influx into mucosa were not observed in rat intestine at 16-17 h p.i. However, considering the findings that the parasite invasion into intestine occurs as early as at 4 h p.i.…”

Host genetic backgrounds: the key to determining parasite-host adaptation

“…Some rodent strains, for example, DBA/2 mice, show higher susceptibility to alveolar echinococcosis than C57BL/6 mice, whereas humans are generally more resistant than nonhuman primates ( Nakao et al., 2011 ; Armua-Fernandez et al., 2016 ). In addition, other immune factors, including neutrophils and MHC polymorphisms, lower the susceptibility to and onset of echinococcosis in the hosts ( Vuitton et al., 2006 ; Joekel et al., 2021 ). Hosts with HLA-DR3 + and HLA-DQ2 + haplotypes are more susceptible to progressive alveolar echinococcosis.…”

Alveolar echinococcosis: what triggers emergence in North America, Central Europe and Asia?

“…However, after immunosuppressive treatment with dexamethasone, rats become susceptible. The key element found were granulocytes (polymorphonuclear cells, PMN), as the majority of PMN-depleted animals developed liver metacestodes within 10 weeks after infection [53 ▪ ]. With regard to full resistance that protects from disease, pigs were shown to be appropriate for studying resistance mechanisms.…”