Kentaro Yoshimura

Ultrastructural evidence for eosinophil-mediated destruction of Angiostrongylus cantonensis transferred into the pulmonary artery of non-permissive hosts

Summary Ultrastructural and cytochemical analyses were carried out on cellular reactions to the young adult worms of Angiostrongylus cantonensis surgically transferred into the pulmonary arteries of permissive (rat) and non‐permissive (rabbit and guinea‐pig) hosts. In permissive hosts, no appreciable cellular reactions could be found around worms throughout the course of the observations. By contrast, the infiltration of neutrophils along with eosinophils was observed around worms in non‐permissive hosts even at early stages (days 2 to 4). At day 7 and later, the prominent degranulation (solubilization of the whole granule or the matrix alone with preserved crystalloid, tubulovesicular structure formation, and vacuole formation containing lysosomal contents, etc.) of eosinophils, and subsequent release of the lysosomal contents on to the worm surface were noted. Discharge of large amounts of peroxidase on to the worm surface was also demonstrated. The worms were thus damaged and their cuticular fragments were frequently found removed. In addition to this, degenerative changes, such as lipid‐droplet and vacuole formations, were detectable in the hypodermis, somatic musculature and intestine of the parasites transferred into the non‐permissive hosts, as early as day 4 after transfer. These data suggest that eosinophils would serve as a potential effector cell for killing of pulmonary arterial A. cantonensis in non‐permissive hosts.

Angiostrongylus cantonensis: development following pulmonary arterial transfers into permissive and nonpermissive hosts.

The survival, growth, and egg-laying capacity of young adult Angiostrongylus cantonensis, surgically transferred from intracranial sites into pulmonary arteries, were studied. A variety of experimental animals (rats, guinea pigs, mice, and mastomys) were chosen as donor animals and as recipient hosts (rats, guinea pigs, and rabbits). These species were specifically chosen to span the spectrum of host permissiveness relative to worm development in an attempt to understand the mechanisms which underlie species-dependent resistance. Recipient animals were monitored not only for the development of parasites per se but also for antibody production and histopathologic changes. The results indicated that these procedures were technically feasible, with good worm development following intra-rat transfers, as early as 15 days after initial exposure. Studies were performed to analyze the constraints of development both on initial, i.e., prelung and subsequent i.e., postlung development. When worms were obtained from permissive species such as rat or mastomys, transfer into rats resulted in good growth and development; however, worms which developed initially in exposed mice or guinea pigs developed less well in the rat. Conversely, worms which developed initially in permissive host such as the rat, when transferred into a variety of less permissive hosts such as the guinea pig and rabbit, apparently did not survive and caused significant morbidity and mortality within the nonpermissive host. Histopathologic evaluation revealed a strong eosinophilic perivascular and peribronchiolar infiltration as well as granulomatous reactions surrounding the worms in the lungs of recipient guinea pigs and rabbits, changes not observed in the lungs of permissive rat recipients. As reaginic antibody responses were also more prominent in nonpermissive than in permissive animals, it is possible that IgE responses may be more directly related to the phenomenon of morbidity and/or permissiveness than are other aspects of immune response. In support of this contention was the finding of nearly equivalent hemagglutinating antibody production between permissive rats and nonpermissive guinea pigs and rabbits.

The course ofAngiostrongylus cantonensis infection in athymic nude and neonatally thymectomized mice

BALB/c athymic nude and thymus-reconstituted nude mice and neonatally thymectomized BALB/c mice were infected with stage 3 larvae ofAngiostrongylus cantonensis and the worm burdens of the mice were determined at various times after infection. When the nude and thymectomized mice were exposed to the parasite, some worms were found to migrate from the brain to lungs but died there without reaching maturity. This pulmonary arterial migration of the worms in the nude mice did not occur following thymic reconstitution. These data suggest that the inability of murine intracranial worms to migrate to the lungs is at least in part due to thymus-dependent mechanisms, and also that the failure of worm maturation in mouse lungs might be due to thymus-independent immune mechanisms and/or nonimmunological mechanisms.

Studies of Angiostrongylus cantonensis in two experimental hosts.

Lung infection with Angiostrongylus cantonensis was established in experimentally infected Indian soft-furred rats (Millardia meltada) and Indian spiny mice (Mus platythrix). Pulmonary arterial migration occurred earlier (at day 20 after infection) in M. meltada than in Wistar rats. M. meltada and M. platythrix could serve as useful animal models for comparative studies of mechanisms determining host specificity of A. cantonensis.

Angiostrongylus cantonensis: Rejection of pulmonary arterial transfers of lung stage worms

Abstract Experimental transfer of the lung stage worms of Angiostrongylus cantonensis was performed between permissive hosts (rats) and between permissive (rat) and nonpermissive hosts (guinea pigs and rabbits). These worms from rats were rejected when implanted into nonpermissive hosts. Unexpectedly, similar worms did not survive well even in permissive hosts; the majority of recipient rats did not have first-stage larvae (L 1 ) in their stools and, even when positive for L 1 , the number of the larvae shed was few. These findings contrast with the successful pulmonary arterial transfer of younger, intracranial-stage worms. It was shown that differences in rat strain between donor and recipient had no significant effect on the subsequent worm survival in recipient hosts. The alteration of maintaining conditions of the intrapulmonary worms, prior to transfer, in terms of temperature, media, and maintaining period, also showed no profound effect on the subsequent worm survival. The kinetics of precipitating and reaginic antibody levels in rats implanted with the intrapulmonary worms were analogous to those in rats with intracranial-stage worms. The findings indicate that some qualitative differences may exist between the worms obtained from two different sites.