Comprehensive immune profiling reveals IFN-? signaling in T cells mediates parasite phagocytosis in a rodent malaria model : Spatial transcriptomics data
Malaria-associated lung pathology, a severe and life-threatening manifestation of Plasmodium infection, involves complex immune remodeling within the pulmonary microenvironment. To resolve the spatial architecture of this immune response, we performed spatial transcriptomic analysis on lung tissues from a Plasmodium berghei NK65-induced rodent model. Our study identifies IFN-? signaling in T cells as a pivotal regulator of the lung's spatial immune landscape. By utilizing conditional knockout (cKO) mice lacking Ifngr1 specifically in T cells, we observed that the blockade of T cell-intrinsic IFN-? signaling attenuates lung pathology. Spatially, this protection is characterized by an enriched colocalization and enhanced interaction between T cells and monocytes. This robust interaction drives the expansion of a unique proinflammatory monocyte subset defined by CD8 and Ly6C expression within specific pulmonary niches. These CD8+ Ly6C+ monocytes exhibit significantly enhanced phagocytic capacity and elevated MHCII expression in situ. Our spatially resolved findings illustrate that the T cell-IFN-? signaling axis dictates the spatial organization of T cell-monocyte communication, highlighting this interaction as a potential therapeutic target for mitigating malaria-induced lung injury. Overall design: To characterize the spatial immune landscape of malaria-associated lung pathology, we performed spatial transcriptomic analysis on lung tissues from naïve, infected (day 7), and T cell-specific Ifngr1 cKO (day 7) mice, with the two infected groups multiplexed onto a single slide to generate two integrated sequencing libraries; this design enables precise in situ mapping of cellular interactions and reveals how the loss of T cell-intrinsic IFN-? signaling reshapes the pulmonary microenvironmental niches to attenuate tissue injury.