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Microglial cells from psychologically stressed mice as an accelerator of cerebral cryptococcosis
Masae Shimoda1, Vickie C Jones, Makiko Kobayashi
1Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas 77555-0435, USA.
Abstract:
Severe stress decreases the resistance of hosts exposed to microbial infections. As compared with two groups of control mice (normal mice, food-and-water-deprived mice [FWD mice]), restraint-stressed mice (RST mice) were shown to be greatly susceptible to intracerebral growth of Cryptococcus neoformans. The susceptibility of FWD mice to cerebral cryptococcosis increased to the level shown in RST mice, when these groups of mice were inoculated with microglial cells from the brains of RST mice. However, the susceptibility of FWD mice to cerebral cryptococcosis was not influenced by the adoptive transfer of microglial cells from normal mice or FWD mice. Microglial cells from RST mice produced CC-chemokine ligand-2 (CCL-2/monocyte chemoattractant protein 1), but not microglial cells from FWD mice. The resistance of RST mice to cerebral cryptococcosis was improved to the extent shown in FWD mice, when they were treated with anti-CCL-2 antibody. However, the susceptibility of normal mice and FWD mice to cerebral cryptococcosis increased to that shown in RST mice, when they were treated with rCCL-2. Microglial cells from RST mice were discriminated from the same cell preparations derived from FWD mice by their abilities to produce CCL-2, to phagocytize C. neoformans cells and to express Toll-like receptor 2. These results indicate that the resistance of RST mice to cerebral cryptococcosis is diminished by CCL-2 produced by microglial cells that are influenced by restraint stress.
Insights
Restraint stress increases susceptibility to Cryptococcus neoformans brain infections. Stress-activated microglial cells produce CC-chemokine ligand-2 (CCL-2), diminishing host resistance.
Area of Science:
- Neuroimmunology
- Infectious Disease Immunology
Background:
- Severe stress compromises host immunity, increasing susceptibility to microbial infections.
- Restraint stress (RST) significantly enhances susceptibility to intracerebral Cryptococcus neoformans infections in mice.
Purpose of the Study:
- To investigate the role of microglial cells and CC-chemokine ligand-2 (CCL-2) in stress-induced susceptibility to cerebral cryptococcosis.
Main Methods:
- Comparative analysis of restraint-stressed (RST) mice, food-and-water-deprived (FWD) mice, and normal mice.
- Adoptive transfer of microglial cells from different mouse groups.
- Treatment with anti-CCL-2 antibody and recombinant CCL-2 (rCCL-2).
- Assessment of microglial cell functions including CCL-2 production, phagocytosis, and Toll-like receptor 2 expression.
Main Results:
- Microglial cells from RST mice produced CCL-2, unlike those from FWD or normal mice.
- Transfer of RST microglial cells increased susceptibility in FWD mice.
- Anti-CCL-2 antibody treatment improved resistance in RST mice.
- rCCL-2 administration increased susceptibility in normal and FWD mice.
- RST-derived microglial cells showed enhanced CCL-2 production, phagocytosis, and Toll-like receptor 2 expression.
Conclusions:
- Restraint stress diminishes host resistance to cerebral cryptococcosis.
- CCL-2 produced by stress-influenced microglial cells plays a critical role in this diminished resistance.
- Microglial cell activation by stress contributes to increased susceptibility to fungal brain infections.
