Infect Immun. 2010 Mar 1. [Epub ahead of print]
CCR7 dependent immunity during acute Toxoplasma gondii infection
Noor S, Habashy AS, Nance JP, Clark RE, Nemati K, Carson MJ, Wilson EH.
Division of Biomedical Sciences, University of California, Riverside, CA 92521, USA.
The chemokine receptor CCR7 is a well established homing receptor for dendritic cells and T cells. Interactions with its ligands CCL19 and CCL21 facilitate priming of immune responses in lymphoid tissue yet CCR7-independent immune responses can be generated in the presence of sufficient antigen. In these studies we investigated the role of CCR7 signaling in the generation of protective immune responses to the intracellular protozoan parasite, Toxoplasma gondii. Results demonstrate a significant increase in the expression of CCL19, CCL21 and CCR7 in peripheral and CNS tissue over the course of infection. Unexpectedly, despite the presence of abundant antigen, CCR7 was an absolute requirement for protective immunity to T. gondii as CCR7(-/-) mice succumbed to the parasite early in the acute phase of infection. Although serum levels of IL-12, IL-6, TNF-alpha, and IL-10 remained unchanged there was a significant decrease in CCL2/MCP-1 and inflammatory monocyte recruitment to the site of infection. In addition, CCR7(-/-) mice failed to produce sufficient IFN-gamma, a critical Th1 associated effector cytokine required to control parasite replication. As a result there was increased parasite dissemination and a significant increase in parasite burden in the lung, liver and brains of infected mice. Adoptive transfer experiments revealed that expression of CCR7 on the T cell compartment alone is sufficient to enable T cell priming, increase IFN-gamma production and allow survival of CCR7(-/-) mice. These data demonstrate an absolute requirement for T cell expression of CCR7 for the generation of protective immune responses to Toxoplasma infection.
PMID: 20194594 [PubMed - as supplied by publisher]