Poster Presentation 8th Australasian Vaccines & Immunotherapeutics Development Meeting 2020

Lung endothelial cell antigen cross-presentation to CD8+ T cells: With an angle to hamper CD8+ T cells pathogenesis in malaria-associated lung injury (#320)

Samantha Nguee 1 2 , Carla Claser 1 , Laurent Renia 1 2
  1. Infectious Diseases Horizontal Technology Centre-Singapore Immunology Network (A*STAR) , Singapore
  2. Microbiology and Immunology, Yong Loo Lin School of Medicine (National University of Singapore), Singapore

Malaria-associated acute lung injury (MA-ALI) is a clinical complication of severe malaria. MA-ALI is characterized by edematous lung, along with marked infiltration of inflammatory cells and damaged alveolar-capillary barrier. However in MA-ALI, the pathogenic mechanisms remain largely unclear. Murine models mimicking MA-ALI in humans are powerful tools to gain insights into the pathogenesis. Here, we show that C57BL/6 mice infected with Plasmodium berghei ANKA (PbA), a murine MA-ALI model, had increased transmigration of total and antigen-specific CD8+ T cells in the lung. Notably, in vivo antibody depletion of CD8+ T cells prevented lung injury. When we transferred antigen-specific CD8+ T cells to PbA-infected TCRβ-/- mice (devoid of functional T cells population), lung vascular leakage was recapitulated. Lastly, we further demonstrated that accumulation of parasitized erythrocytes led to lung endothelium cross-presentation of parasite antigen to antigen-specific CD8+ T cells, a process dependent on IFNg. In summary, lung vascular injury in MA-ALI is a consequence of the chronological occurrence of parasitized erythrocytes in the lung microvasculature, followed by antigen capture and processing by the activated endothelium, which cross-presents to antigen-specific CD8+ T cells infiltrated in the lung during PbA infection.