Comprehensive immune profiling reveals IFN-γ signaling in T cells mediates parasite phagocytosis in a rodent malaria model : Bulk RNA-seq

Pulmonary manifestations are life-threatening complications of malaria. To elucidate the immune landscape underlying malaria-associated lung pathology, we performed comprehensive transcriptomic analyses using a rodent malaria model. We identified that IFN-γ signaling specifically in T cells is a critical regulator of lung pathology. Our data demonstrate that the disruption of IFN-γ signaling in T cells results in reduced pulmonary parasite load and attenuated lung injury by enhancing T cell-monocyte interactions. Notably, this enhanced interaction promotes the expansion of a specific proinflammatory monocyte subset characterized by CD8 and Ly6C expression. This CD8+ Ly6C+ monocyte population exhibits significantly higher phagocytic capacity compared to its CD8− counterpart. Our study highlights the complex immune network induced by Plasmodium infection and reveals the essential role of the T cell-IFN-γ signaling axis in modulating monocyte-mediated parasite clearance and lung pathology.