Lung endothelial cell antigen cross-presentation to CD8+T cells drives malaria-associated lung injury
| Autor: | Jacqueline Theng Theng Ho, Bavani Gunasegaran, Laurent Rénia, Julian L. Goggi, Shanshan W. Howland, Carla Claser, Lai Guan Ng, Samantha Yee Teng Nguee, Chee Bing Ong, Siddesh V. Hartimath, Evan W. Newell, Audrey W. Q. Lee, Etienne Becht, Akhila Balachander |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
ARDS Science Antigen-presenting cells General Physics and Astronomy Lung injury Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Antigen parasitic diseases Medicine Cytotoxic T cell lcsh:Science Multidisciplinary Lung biology business.industry General Chemistry medicine.disease Cellular immunity Malaria Endothelial stem cell 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology biology.protein lcsh:Q Antibody business CD8 Parasite host response |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-16 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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