Physiological microbial exposure normalizes memory T cell surveillance of the brain and modifies host seizure...

Area of Science:

• Neuroimmunology
• T cell biology
• Microbial immunology

Background:

• Recent research indicates memory T cells reside in the human brain, with some targeting peripheral infections.
• The origin and function of these brain-resident memory T cells remain largely unknown.
• Understanding their source is crucial for investigating neurological health and disease.

Purpose of the Study:

• To investigate the origins of brain T cells by modeling peripheral microbial exposure in mice.
• To determine the impact of microbial exposure on brain T cell populations and function.
• To explore the role of memory T cells in modulating brain biology and neurological conditions.

Main Methods:

• Utilized two models of polymicrobial exposure (cohousing and sequential infection) in specific pathogen-free mice.
• Analyzed T cell populations within brain tissue and characterized their localization and interactions with myeloid cells.
• Induced seizures to assess the functional state of brain-localized memory T cells and their impact on seizure duration.

Main Results:

• Cohousing and sequential infection models significantly increased memory T cell numbers in mouse brain tissue.
• Resident and circulating memory T cells were found in various brain regions, interacting with myeloid cells.
• Microbial exposure led to altered function of brain T cells following induced seizures and influenced seizure duration.

Conclusions:

• Peripheral microbial exposure can lead to the accumulation and functional modulation of memory T cells in the brain.
• These findings suggest a potential origin for brain-resident memory T cells observed in humans.
• Microbe-experienced mice serve as a valuable model for studying the influence of T cells on neurological health and disease.