Lung macrophages control malaria-induced pulmonary inflammation (56.17)

Abstract

Abstract Pulmonary edema and acute respiratory distress are archetypal symptoms of severe malaria that occur in ~20% of patients and are associated with mortality rates exceeding 70%. Little is known about the pathogenesis of lung pathology associated with Plasmodium infections. We tested the hypothesis that two major cellular populations - CD11c+CD11b- resident macrophages and CD11b+Ly6C+ recruited monocytes/macrophages - are key players in regulating the nature and magnitude of malaria-induced pulmonary pathology. During the very early stages of Plasmodium berghei infections in mice, parasites are taken up by resident macrophages. This is associated with the transient activation of resident macrophages and the release of chemokines that recruit large numbers of CD11b+Ly6C+ blood monocytes. Flow cytometry results suggest that later in infection resident lung macrophages take on a regulatory phenotype, while the recruited monocytes undergo activation, differentiation into macrophages and are responsible for the majority of parasite clearance within the lungs. Administration of a blocking monoclonal antibody (anti-CD11b; 5C6) diminishes the homing of monocytes to the lungs, resulting in decreased parasite uptake. We propose that both myeloid populations control pulmonary inflammation through the clearance of sequestered parasites within the pulmonary microvasculature as well as the regulation of pro-inflammatory processes within the lung environment.