Abstract

Pulmonary manifestation in malaria can be life-threatening. Using a rodent malaria model and comprehensive transcriptomics analyses to illustrate the immune landscape of malaria-associated lung pathology, we identified that IFN-γ signaling in T cells plays an important role in malaria-associated lung pathology. Disruption of IFN-γ signaling in T cells leads to reduced parasite load in the lungs and attenuated lung pathology by enhancing T cell-monocyte interaction. Surprisingly, the stronger interaction leads to an increase in a proinflammatory monocyte subset characterized by CD8 and Ly6C expression, which exhibits prominently elevated phagocytic capacity compared to the CD8− counterpart. Our study illustrates the importance of IFN-γ signaling in T cell-monocyte interaction in malaria-associated lung pathology, highlighting the complex and intricate immune network induced by the Plasmodium infection.