PATHOGENIC ROLE OF CD8+ T CELLS IN MALARIA-ASSOCIATED ACUTE LUNG INJURY IN MICE

Abstract

Malaria-associated lung injury (MA-ALI/ARDS) is a clinical complication of severe malaria. MA-ALI/ARDS is characterized by damaged alveolar-capillary barrier along with marked infiltration of inflammatory cells. However, in MA-ALI/ARDS, the pathogenic mechanisms and their chronology remain largely unclear. In <em>Plasmodium berghei ANKA</em> infected-C57BL/6 mice, we identified CD8+ T cells as the main pathogenic effector in the lung. We demonstrated that with accumulated parasitized erythrocytes in the microvasculature, the activated lung endothelium can cross-present the parasite antigen to parasite-specific CD8+ T cells, a process dependent on IFNγ. We demonstrated that priming of CD8+ T cells required at least CD86-mediated co-stimulation with CD28 in the spleen for its effector functions in the lung to cause injury. In summary, MA-ALI/ARDS is due to the accumulation of parasitized erythrocytes in the lung microvasculature, followed by antigen capture and processing by the activated endothelium, which cross-presents to parasite-specific CD8+ T cells infiltrated in the lung.