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

Paul M. Robben, Marie LaRegina, William A. Kuziel, L. David Sibley

Research output: Contribution to journalArticlepeer-review

216 Scopus citations

Abstract

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-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 ay be an important general mechanism for resistance to intracellular pathogens. JEM

Original languageEnglish
Pages (from-to)1761-1769
Number of pages9
JournalJournal of Experimental Medicine
Volume201
Issue number11
DOIs
StatePublished - Jun 6 2005

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