RESUMO
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-CD8ß 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 TCRß-/- 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.
Assuntos
Lesão Pulmonar Aguda/patologia , Linfócitos T CD8-Positivos/imunologia , Apresentação Cruzada/imunologia , Interferon gama/imunologia , Malária/imunologia , Síndrome do Desconforto Respiratório/patologia , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/parasitologia , Animais , Modelos Animais de Doenças , Células Endoteliais/imunologia , Feminino , Pulmão/parasitologia , Pulmão/patologia , Malária/tratamento farmacológico , Malária/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Plasmodium berghei/imunologia , Edema Pulmonar/parasitologia , Edema Pulmonar/patologia , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/parasitologiaRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.