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

• Published in: The Journal of experimental medicine 2005-06, Vol.201 (11), p.1761-1769
• Main Authors: Robben, Paul M, LaRegina, Marie, Kuziel, William A, Sibley, L David
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Antigens, CD - genetics; Antigens, CD - immunology; Cell Movement - genetics; Cell Movement - immunology; Chemokine CCL2 - genetics; Chemokine CCL2 - immunology; CX3C Chemokine Receptor 1; Cytokines - immunology; Host-Parasite Interactions - genetics; Host-Parasite Interactions - immunology; Mice; Mice, Knockout; Monocytes - immunology; Receptors, CCR2; Receptors, Chemokine - genetics; Receptors, Chemokine - immunology; Th1 Cells - immunology; Toxoplasma - immunology; Toxoplasmosis, Animal - genetics; Toxoplasmosis, Animal - immunology; Toxoplasmosis, Animal - pathology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20050054

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.