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(-)/CX3CR1high) or responding to sites of inflammation ( Gr-1(+)/CCR2(+)/CX3CR1lo). 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-alpha, and IFN-gamma. 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.