Lung endothelial cell antigen cross-presentation to CD8+T cells drives malaria-associated lung injury

Carla Claser (), Samantha Yee Teng Nguee, Akhila Balachander, Shanshan Wu Howland, Etienne Becht, Bavani Gunasegaran, Siddesh V. Hartimath, Audrey W. Q. Lee, Jacqueline Theng Theng Ho, Chee Bing Ong, Evan W. Newell, Julian Goggi, Lai Guan Ng and Laurent Renia ()
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Carla Claser: A*STAR, 8A Biomedical Grove
Samantha Yee Teng Nguee: A*STAR, 8A Biomedical Grove
Akhila Balachander: A*STAR, 8A Biomedical Grove
Shanshan Wu Howland: A*STAR, 8A Biomedical Grove
Etienne Becht: A*STAR, 8A Biomedical Grove
Bavani Gunasegaran: A*STAR, 8A Biomedical Grove
Siddesh V. Hartimath: Singapore Bioimaging Consortium (SBIC), A*STAR
Audrey W. Q. Lee: A*STAR, 8A Biomedical Grove
Jacqueline Theng Theng Ho: A*STAR, 8A Biomedical Grove
Chee Bing Ong: Institute of Molecular and Cell Biology (IMCB), A*STAR
Evan W. Newell: A*STAR, 8A Biomedical Grove
Julian Goggi: Singapore Bioimaging Consortium (SBIC), A*STAR
Lai Guan Ng: A*STAR, 8A Biomedical Grove
Laurent Renia: A*STAR, 8A Biomedical Grove

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: 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-CD8β 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 TCRβ−/− 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 IFNγ−dependent manner. In conclusion, pulmonary vascular damage in ALI is a consequence of IFNγ-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.

Date: 2019
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DOI: 10.1038/s41467-019-12017-8

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