Regulatory T cells in microbial infection.

Area of Science:

• Immunology
• Cellular Biology

Background:

• Natural T regulatory cells (NatTReg) are crucial for limiting immune pathology during infections.
• Infection paradoxically increases NatTReg numbers and activity, requiring reconciliation with self-non-self discrimination principles.
• Existing evidence suggests NatTReg involved in infection responses originate from the autoreactive repertoire.

Purpose of the Study:

• To reconcile the role of NatTReg in infection with their function in self-tolerance.
• To explain the 'hygiene hypothesis' through the lens of NatTReg expansion.
• To explore the molecular mechanisms underlying NatTReg activation and expansion during infection.

Main Methods:

• Review of existing scientific literature and evidence.
• Analysis of the 'self-nonself' discrimination process in relation to NatTReg function.
• Examination of the role of Toll-like receptor ligands and cytokines (IL-2/IL-15) in NatTReg activation.

Main Results:

• NatTReg involved in infection responses are largely autoreactive, supporting the 'hygiene hypothesis'.
• Pro-inflammatory ligands from Toll-like receptors (microbial and endogenous) are critical for NatTReg activation and expansion.
• NatTReg respond to locally produced IL-2/IL-15, creating a feedback loop to limit tissue damage.

Conclusions:

• Infections enhance natural tolerance by expanding NatTReg, which are primarily autoreactive.
• Toll-like receptor signaling and cytokine responses orchestrate NatTReg expansion for immune homeostasis.
• Understanding these mechanisms offers potential therapeutic targets for autoimmune diseases, allergies, chronic infections, and cancer.