The role of pulmonary cellular reactions in the resistance of vaccinated mice to Schistosoma mansoni

Abstract

A histopathological and ultrastructural study was made of schistosomula and associated inflammatory reactions in the lungs of normal mice, and mice previously vaccinated with irradiated cercariae. In normal mice at day 7 post-infection all schistosomula were located in blood vessels. From day 11 onwards an increasing proportion of schistosomula were intra-alveolar (80% from day 20). No cellular reactions were evident around intravascular parasites in normal mice but at later sampling times large compact foci were associated with alveolar parasites. Initial reactions, probably in response to non-specific tissue damage, were approximately 50% polymorphonuclear, and 50% mononuclear. Mononuclear cells predominated at later times. In spite of inflammation, no damage to the schistosomula was observed. There was no evidence for re-entry of schistosomula into blood vessels, and it was assumed entry into alveoli occurred accidentally as parasites attempted to traverse pulmonary blood vessels. The pattern of localization of schistosomula in vaccinated mice was similar to that in normal mice, the proportion in alveoli increasing with time (64% from day 20). The most significant difference was that intravascular schistosomula attracted foci of host leucocytes which were always 85% or more mononuclear, containing both lymphocytes and macrophages. The infiltrating cells enlarged the intersititium, separating the vascular endothelium from the alveolar epithelium. Fibrous protein was also deposited in the interstitial region. In some instances the complete blood-air barrier was destroyed by the infiltrates. Unusual paracrystalline inclusions were observed in alveolar macrophages and giant cells. The differences in cellular responses in vaccinated and normal mice suggest that challenge schistosomula stimulated an anamnestic immune response. The resulting inflammation, by impeding movement through the vasculature, terminated migration in the lungs, and accounted for the observed resistance to reinfection. The reactions in vaccinated mice have many of the features of a delayed hypersensitivity response implying that lung phase resistance in vaccinated mice may be T-cell rather than antibody-mediated.

Endothelial cells are activated by cytokine treatment to kill an intravascular parasite, Schistosoma mansoni, through the production of nitric oxide.

“…To evaluate the relevance of these in vitro observations to immunity in vivo, we examined morphologic changes in the lungs of mice vaccinated with radiation-attenuated parasites after challenge infection. In addition to the presence of inflammatory foci in the lung parenchyma previously described (5,15), remarkable endarteritis and periarteritis were observed, with mononuclear cell and eosinophil infiltration.…”

“…On day 21 after infection, most of the larvae detectable in the lungs of vaccinated mice are located within blood vessels, although -25% are found within alveolar spaces. About half of the identifiable larvae in either site are surrounded by moderate to intense inflammatory reactions consisting mostly of mononuclear cells (15,16).…”

Radiation-attenuated schistosome vaccination – a brief historical perspective

“…Regarding the mechanism of antibody-mediated attrition, mice vaccinated with repeat (2 or 3) exposures and in which antibody is believed to play a key role, show essentially similar mononuclear cellrich foci around challenge LS in the lung Kassim et al 1992) as have been described for singly vaccinated mice (Crabtree and Wilson, 1986). Again the larvae appear undamaged and a proportion of them occur within alveoli, in which case they induce marked inflammatory responses (Kassim et al 1992).…”

“…Cells accumulate within the blood vessel and between the vascular endothelium and the alveolar epithelium resulting, it is suggested, in the intravascular migration of the larvae being impeded. Certainly, with time, an increasing proportion of larvae occur within alveoli where they induce even more pronounced foci (Crabtree and Wilson, 1986). Although Von Lichtenberg et al (1985) described damaged LS in vaccinated mice, Crabtree and Wilson (1986) found no evidence of parasite damage and this led to the notion that LS may not be killed within the lung but rather diverted from their intravascular migration into the alveoli and subsequently lost via the trachea and eventually the GI tract.…”

“…Certainly, with time, an increasing proportion of larvae occur within alveoli where they induce even more pronounced foci (Crabtree and Wilson, 1986). Although Von Lichtenberg et al (1985) described damaged LS in vaccinated mice, Crabtree and Wilson (1986) found no evidence of parasite damage and this led to the notion that LS may not be killed within the lung but rather diverted from their intravascular migration into the alveoli and subsequently lost via the trachea and eventually the GI tract. This was supported by later studies showing that challenge LS recovered from lungs of vaccinated mice over the extended period of attrition showed normal viability when injected into naïve mice .…”