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- Title
Lung endothelial cell antigen cross-presentation to CD8<sup>+</sup>T cells drives malaria-associated lung injury.
- Authors
Claser, Carla; Nguee, Samantha Yee Teng; Balachander, Akhila; Wu Howland, Shanshan; Becht, Etienne; Gunasegaran, Bavani; Hartimath, Siddesh V.; Lee, Audrey W. Q.; Theng Theng Ho, Jacqueline; Bing Ong, Chee; Newell, Evan W.; Goggi, Julian; Guan Ng, Lai; Renia, Laurent
- 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. Severe malaria can be associated with respiratory complications. Here, the authors show that malaria-associated pulmonary vascular damage 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.
- Subjects
ENDOTHELIAL cells; ERYTHROCYTES; PARASITE antigens; ADULT respiratory distress syndrome; LUNG injuries; LUNGS
- Publication
Nature Communications, 2019, Vol 10, Issue 1, pN.PAG
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-019-12017-8