M1 macrophage activation in severe Plasmodium falciparum malaria patients with pulmonary oedema

Abstract

Background Pulmonary oedema (PE) is a serious complication of severe P. falciparum malaria which can lead to acute lung injury in severe cases. Lung macrophages are activated during malaria infection due to a complex host-immune response. The molecular basis for macrophage polarisation is still unclear but understanding the predominant subtypes could lead to new therapeutic strategies where the diseases present with lung involvement. The present study was designed to study the polarisation of lung macrophages, as M1 or M2 macrophages, in the lungs of severe P. falciparum malaria patients with and without evidence of PE.Methods Lung tissue samples, taken from patients who died from severe P. falciparum malaria, were categorised into severe malaria with PE and without PE (non-PE). Expression of surface markers (CD68-all macrophages, CD40-M1 macrophage and CD163-M2 macrophage) on activated lung macrophages was used to quantify M1/M2 macrophage subtypes. ResultsLung injury was demonstrated in malaria patients with PE. The expression of CD40 (M1 macrophage) was prominent in the group of severe P. falciparum malaria patients with PE (p < 0.05), whereas there was no difference observed for CD163 (M2 macrophage) between PE and non-PE groups. ConclusionsThe study demonstrates M1 polarisation in lung tissues from severe P. falciparum malaria infections with PE. Understanding the nature of macrophage characterisation in malaria infection may provide new insights into therapeutic approaches that could be deployed to reduce lung damage in severe P. falciparum malaria. BackgroundPulmonary oedema (PE) is one of the major complications and therapeutic challenges in severe P. falciparum malaria. This condition is associated with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) [1]. The incidence of ARDS in severe P. falciparum patients ranges from 14%-26%, with the mortality rate of 14%-89% [2][3][4]. In addition, PE occurs in approximately 10%-21% [1,5, 6]. In P. falciparum malaria, PE is associated with inflammatory infiltrates consisting of mainly mononuclear cells, haemozoin deposit, the accumulation of macrophages, as well as parasite