Ly6Chigh Monocytes Control Cerebral Toxoplasmosis

J Immunol. 2015 Feb 20. pii: 1402037. [Epub ahead of print]

 

Biswas A¹, Bruder D², Wolf SA³, Jeron A¹, Mack M⁴, Heimesaat MM⁵, Dunay IR⁶.

 

Cerebral infection with the parasite Toxoplasma gondii is followed by activation of resident cells and recruitment of immune cells from the periphery to the CNS. In this study, we show that a subset of myeloid cells, namely Ly6C^highCCR2⁺ inflammatory monocytes that infiltrate the brain upon chronic T. gondii infection, plays a decisive role in host defense. Depletion of this monocyte subset resulted in elevated parasite load and decreased survival of infected mice, suggesting their crucial role. Notably, Ly6C^highCCR2⁺ monocytes governed parasite control due to production of proinflammatory mediators, such as IL-1α, IL-1β, IL-6, inducible NO synthase, TNF, and reactive oxygen intermediate. Interestingly, Ly6C^highCCR2⁺ monocytes were also able to produce the regulatory cytokine IL-10, revealing their dual feature. Moreover, we confirmed by adoptive transfer that the recruited monocytes further develop into two distinct subpopulations contributing to parasite control and profound host defense. The differentiated Ly6C^intCCR2⁺F4/80^int subset upregulated MHC I and MHC II molecules, suggesting dendritic cell properties such as interaction with T cells, whereas the Ly6C^negF4/80^high cell subset displayed elevated phagocytic capacity while upregulating triggering receptor expressed on myeloid cells-2. Finally, we have shown that the recruitment of Ly6C^high monocytes to the CNS is regulated by P-selectin glycoprotein ligand-1. These results indicate the critical importance of recruited Ly6C^high monocytes upon cerebral toxoplasmosis and reveal the behavior of further differentiated myeloid-derived mononuclear cell subsets in parasite control and immune regulation of the CNS.
Copyright © 2015 by The American Association of Immunologists, Inc.

PMID:

25710908

[PubMed - as supplied by publisher]