Lung-phase immunity to Schistosoma mansoni. Flow cytometric analysis of macrophage activation states in vaccinated mice

Abstract

A delayed-type hypersensitivity response has been postulated as the effector mechanism of lung-phase immunity to Schistosoma mansoni. We have sought evidence for this response by examining the state of alveolar macrophage activation in C57BL/6 mice vaccinated with radiation-attenuated cercariae, and challenged with normal parasites. As an index of activation, the capacity of macrophages to produce an oxidative burst upon stimulation with PMA, was measured at the single cell level by a flow cytometric method. Fourteen to 28 days after vaccination with 20-kr parasites, highly activated macrophages were recovered from the airways by bronchoalveolar lavage. Their probable role in resistance is to recruit T lymphocytes and macrophages to "arm" the lungs against subsequent challenge. The level of macrophage activation had declined to near background by the time challenge parasites arrived, although pulmonary leucocyte numbers remained elevated. Activated alveolar macrophages were not detected after vaccination with 80-kr parasites, which fail to reach the lungs or induce resistance. Challenge parasites, arriving in the lungs of 20-kr vaccinated mice, stimulated a rapid increase in the activation state of recruited macrophages, coincident with their retention in the pulmonary vasculature. These events occurred later in challenge control mice, with peak activation at day 21, when migration of parasites to the liver is complete. Mice vaccinated with 80-kr parasites lacked the accelerated response to challenge, behaving like the control group. The absence of activated peritoneal macrophages suggests a response restricted to organs such as the lungs, through which both vaccinating and challenge parasites migrate. We suggest that the role of activated alveolar macrophages in lung-phase immunity is to initiate and maintain the focal inflammatory responses which block onward migration of parasites and lead to their demise.