Kinetics and mechanism of effector focus formation in the lungs of mice vaccinated with irradiated cercariae of Schistosoma mansoni

Abstract

The sequence of events involved in effector focus formation around challenge schistosomula in the lungs of mice vaccinated with radiation-attenuated cercariae of Schistosoma mansoni has been characterized following intravenous administration of lung stage larvae. Histopathological analysis of the lungs of vaccinated animals revealed that infiltrating cells were present around larvae within 24 h. The main increment in cell recruitment occurred between 2 and 4 days, with foci reaching maximal diameter on day 8. No additional infiltration of the airways was detected by bronchoalveolar sampling before day 4 when the maximum number of cells, predominantly lymphocytes, was recovered. In contrast, responses in challenge control animals were relatively slight prior to day 12. IFN gamma was the major cytokine in airway cultures from vaccinated mice, the greatest increment in production coinciding with peak cell recruitment. A similar pattern of IFN gamma mRNA expression was observed in whole lung extracts, highlighting the dominance of Th1 responses in the effector mechanism. The slow start to focus formation may be due to the need for antigen, released by the intravascular parasite, to be translocated across the endothelium, processed by accessory cells and presented to the helper T cells which orchestrate the effector mechanism. The delay is of the same order as the period of development which the parasite must undergo in the lung, to facilitate further migration. This similarity in the timing may explain why some larvae are able to avoid the consequences of the pulmonary effector response.