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.
Robben
Paul M
PM
Department of Molecular Microbiology, Center for Infectious Diseases, St. Louis, MO 63110, USA.
LaRegina
Marie
M
Kuziel
William A
WA
Sibley
L David
LD
D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006790:Host-Parasite Interactions / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000276:immunology* / Q000473:pathology
D015703:Antigens, CD; D000073883:CX3C Chemokine Receptor 1; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; C471885:Cx3cr1 protein, mouse; D016207:Cytokines; C503133:Gr-1 protein, mouse; D054390:Receptors, CCR2; D019707:Receptors, Chemokine