Recruitment of Gr-1⁺ monocytes is essential for control of acute toxoplasmosis

Circulating murine monocytes comprise two largely exclusive subpopulations that are responsible for seeding normal tissues (Gr-1⁻/CCR2⁻/CX₃CR1^high) or responding to sites of inflammation (Gr-1⁺/CCR2⁺/CX₃CR1^lo). Gr-1⁺ monocytes are recruited to the site of infection during the early stages of immune response to the intracellular pathogen Toxoplasma gondii. A murine model of toxoplasmosis was thus used to examine the importance of Gr-1⁺ monocytes in the control of disseminated parasitic infection in vivo. The recruitment of Gr-1⁺ monocytes was intimately associated with the ability to suppress early parasite replication at the site of inoculation. Infection of CCR2^−/− and MCP-1^−/− mice with typically nonlethal, low doses of T. gondii resulted in the abrogated recruitment of Gr-1⁺ monocytes. The failure to recruit Gr-1⁺ monocytes resulted in greatly enhanced mortality despite the induction of normal Th1 cell responses leading to high levels of IL-12, TNF-α, and IFN-γ. The profound susceptibility of CCR2^−/− mice establishes Gr-1⁺ monocytes as necessary effector cells in the resistance to acute toxoplasmosis and suggests that the CCR2-dependent recruitment of Gr-1⁺ monocytes may be an important general mechanism for resistance to intracellular pathogens.