CCR2 Receptor Is Essential to Activate Microbicidal Mechanisms to Control Toxoplasma gondii Infection in the Central Nervous System

Abstract

Chemokines comprise a structurally related family of cytokines that regulate leukocyte trafficking. Because infection with Toxoplasma gondii can induce an important inflammatory reaction that, if left uncontrolled, can lead to death, we investigated the role of the chemokine receptor CCR2 in T. gondii infection. We orally infected CCR2 ؊/؊ mice with five ME-49 T. gondii cysts and monitored morbidity, survival, and immune response thereafter. The CCR2 ؊/؊ mice displayed higher susceptibility to infection as all mice died on day 28 after infection. Despite similar Th1 responses, a more evident anti-inflammatory response was induced in the peripheral organs of CCR2 ؊/؊ mice compared with wild-type C57BL/6 mice. Additionally, CCR2؊/؊ mice presented greater parasitism and a milder inflammatory reaction in their peripheral organs with lesser CD4 ؉ and MAC-1 ؉ and greater CD8 ؉ cell migration. The parasite load decreased in these organs in CCR2 ؊/؊ mice but remained uncontrolled in the central nervous system. Additionally, we observed down-regulated inducible nitric oxide synthase expression in peripheral organs from CCR2 ؊/؊ mice that was associated with a small nitric oxide production by spleen macrophages. In conclusion, in the absence of CCR2, another mechanism is activated to control tissue parasitism in peripheral organs. Nevertheless, CCR2 is essential for the activation of microbicidal mediators that control T. gondii replication in the central nervous system.

CCR5 Controls Immune and Metabolic Functions during Toxoplasma gondii Infection

“…We observed an increase in the expression of CCR1, CCR2, CCR4 and CXCR3 in the ileum and liver of infected mice (Figure 1A), as reported previously by our research group and others [12], [22], [23]. In addition, a concomitant down regulation of the Th2-related receptor CCR3 was observed in T. gondii infected mice, in accordance to the fact that eosinophils, mast cells or basophils are not the main leukocytes required for the control of this intracellular parasite.…”

Aryl Hydrocarbon Receptor-Null Allele Mice Have Hematopoietic Stem/Progenitor Cells with Abnormal Characteristics and Functions

“…Notably, CXCR2 KO mice, although reported to be healthy, also develop splenomegaly [29]. CCL2 (MCP-1) is a chemokine secreted by a variety of cells for the recruitment of monocytes, and in its absence, mice show increased susceptibility to a variety of infections including parasitic infections (eg, Toxoplasma gondii infection) [31]. In a recent study, AhR-KO mice were found to be more susceptible to T. gondii infection [32].…”

Congenital toxoplasmosis: candidate host immune genes relevant for vertical transmission and pathogenesis

“…13,14 Other CCRs, such as CCR1, CCR2 and CXCR2, have important roles in neutrophil proliferation and monocyte recruitment, which are essential for parasite control. [15][16][17][18] An early Th2 phenotype (driven by IL-4) is associated with bad outcome. 19,20 Antibodies and their Fc receptors (FcRs) have important roles as well.…”