Regulation of microglial cell responses in murine Toxoplasma encephalitis by CD200/CD200 receptor interaction
Martina Deckert1, Jonathon D Sedgwick, Elena Fischer
1Department of Neuropathology, University of Cologne, Kerpener Strasse 62, 50924, Cologne, Germany. neuropatho@uni-koeln.de
Abstract:
Under autoimmune inflammatory conditions within the brain, evidence suggests that neurons downregulate microglial activation through CD200/CD200R interaction, which reduces disease severity. To gain insight into the regulation of intracerebral immune reactions by resident brain cells in chronic cerebral infections, the expression of the CD200 antigen and the CD200R as well as the functional role of CD200/CD200R interactions were characterized in murine Toxoplasma encephalitis. In the normal brain of C57BL/6 wild type mice, CD200 was ubiquitously expressed on neurons, their axons, cerebral endothelial cells, and plexus macrophages. CD200R was expressed at very low levels on cerebral macrophages and microglia without differences between CD200-/- and wild type mice. Infection of C57BL/6 mice with Toxoplasma gondii induced an upregulation of CD200R on microglia and of CD200 on blood vessel endothelial cells. In Toxoplasma encephalitis of CD200-/- mice, microglial cell numbers strongly increased due to an enhanced proliferation indicated by increased Ki-67 immunoreactivity. In addition, microglial activation was increased in CD200-/- mice as evidenced by a further upregulation of already high MHC class II levels as well as an increased expression of the anti-parasitic effector molecules, TNF and iNOS. The increased microglial cell activation resulted in a reduced intracerebral parasite burden and an increased survival rate. Thus, in Toxoplasma encephalitis, microglial activity was regulated via CD200/CD200R-mediated interaction further pointing to an intrinsic regulation of brain resident cells under inflammatory CNS conditions.
Insights
Neurons regulate brain immune cells via CD200/CD200R signaling. In Toxoplasma encephalitis, lacking CD200 (CD200-/- mice) enhances microglial activation, reducing parasite load and improving survival.
Area of Science:
- Neuroimmunology
- Infectious Diseases
Background:
- Neurons can suppress microglial activation via CD200/CD200R signaling, reducing brain inflammation.
- Understanding intracerebral immune regulation by resident cells is crucial for chronic infections.
Purpose of the Study:
- To investigate CD200 and CD200R expression and function in murine Toxoplasma encephalitis.
- To elucidate the role of CD200/CD200R interactions in regulating microglial responses during chronic cerebral infection.
Main Methods:
- Characterization of CD200 and CD200R expression in normal and infected mouse brains.
- Analysis of microglial proliferation, activation, and parasite burden in CD200-/- and wild-type mice with Toxoplasma encephalitis.
Main Results:
- CD200 is widely expressed in normal brain neurons and vasculature; CD200R is low on microglia.
- Toxoplasma infection upregulated CD200R on microglia and CD200 on endothelial cells.
- CD200 deficiency (CD200-/-) led to increased microglial proliferation and activation (MHC class II, TNF, iNOS).
- Enhanced microglial activation in CD200-/- mice reduced parasite burden and increased survival.
Conclusions:
- CD200/CD200R interaction intrinsically regulates microglial activity in Toxoplasma encephalitis.
- This pathway highlights a mechanism for brain resident cells to control immune responses in the central nervous system (CNS) under inflammatory conditions.
