Toxoplasma gondii parasites induce a localized myeloid cell immune response surrounding parasites in the brain during acute infection

Toxoplasma gondii is a foodborne intracellular parasite that chronically infects the brain. Although T. gondii infection elicits a protective immune response, the nature of the monocyte response in the immediate vicinity of parasites during initial brain infection is not well understood. By infecting mice with T. gondii and comparing areas of the brain containing or not containing parasites, we found an increase in CCR2⁺ monocytes, IBA1⁺ myeloid cells, GFAP⁺ astrocytes, and CD68⁺ signal near parasites in the brain, indicating immune cell infiltration and phagolysosomal activation in response to the infection. CCR2⁺CD68⁺ monocytes were specifically increased near tachyzoites with minimal localization of these cells near cysts in the brain. This monocyte response was also detected near parasite-interacted cells, identified using T. gondii parasites that inject Cre recombinase into “interacted” cells of Ai6 CCR2^RFP/+ mice, enabling us to track these events in vivo. The chemokine CCL2 and its transcription factor NF-κB were also upregulated surrounding parasites in the brain; however, the T. gondii effector protein GRA15, which sustains NF-κB activation in infected cells, was not required for CCL2 production, NF-κB activation, or myeloid cell recruitment to parasites in the brain. In contrast, active T. gondii replication played a more significant role, as CCR2⁺ monocytes were recruited to replication-competent but not replication-deficient T. gondii delivered via intracranial injection into mice. These findings provide novel insights into the drivers of immune cell mobilization and activation in the brain during initial T. gondii central nervous system infection and highlight the importance of parasite replication in this process.