Lung endothelial cell antigen cross-presentation to CD8+T cells drives malaria-associated lung injury
Claser, C. Nguee, S.Y.T. Balachander, A. Wu Howland, S. Becht, E. Gunasegaran, B. Hartimath, S.V. Lee, A.W.Q. Theng Theng Ho, J. Bing Ong, C.
Claser, C.
Nguee, S.Y.T.
Balachander, A.
Wu Howland, S.
Becht, E.
Gunasegaran, B.
Hartimath, S.V.
Lee, A.W.Q.
Theng Theng Ho, J.
Bing Ong, C.
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Alternative Title
Abstract
Malaria-associated acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are life-threatening manifestations of severe malaria infections. The pathogenic mechanisms that lead to respiratory complications, such as vascular leakage, remain unclear. Here, we confirm that depleting CD8+T cells with anti-CD8? antibodies in C57BL/6 mice infected with P. berghei ANKA (PbA) prevent pulmonary vascular leakage. When we transfer activated parasite-specific CD8+T cells into PbA-infected TCR??/? mice (devoid of all T-cell populations), pulmonary vascular leakage recapitulates. Additionally, we demonstrate that PbA-infected erythrocyte accumulation leads to lung endothelial cell cross-presentation of parasite antigen to CD8+T cells in an IFN??dependent manner. In conclusion, pulmonary vascular damage in ALI is a consequence of IFN?-activated lung endothelial cells capturing, processing, and cross-presenting malaria parasite antigen to specific CD8+T cells induced during infection. The mechanistic understanding of the immunopathogenesis in malaria-associated ARDS and ALI provide the basis for development of adjunct treatments. © 2019, The Author(s).
Keywords
Source Title
Nature Communications
Publisher
Nature Publishing Group
Series/Report No.
Collections
Rights
Attribution 4.0 International
Date
2019
DOI
10.1038/s41467-019-12017-8
Type
Article