Intestinal immunopathology is associated with decreased CD73-generated adenosine during lethal infection

Area of Science:

• Immunology
• Gastroenterology
• Molecular Biology

Background:

• Extracellular ATP breakdown by CD39 and CD73 generates immunosuppressive adenosine, crucial for regulating inflammation.
• The gastrointestinal tract's high ATP levels, influenced by commensal bacteria, highlight the importance of adenosinergic control.
• CD4(+) T lymphocytes, including conventional (Tconv) and regulatory (Treg) cells, play key roles in intestinal immune homeostasis.

Purpose of the Study:

• To investigate the role of adenosinergic regulation in the mouse intestine under steady-state and during acute Toxoplasma gondii infection.
• To determine the expression and function of CD39 and CD73 on intestinal T lymphocytes.
• To explore the therapeutic potential of adenosine receptor agonists in managing intestinal inflammation.

Main Methods:

• Flow cytometry to analyze CD39 and CD73 expression on intestinal CD4(+) T cells.
• Induction of acute Toxoplasma gondii infection in mice.
• Administration of adenosine receptor agonists to assess their impact on immunopathology and gut microbiota.

Main Results:

• Both Tconv and Treg CD4(+) T lymphocytes express CD39 and CD73 in the naive mouse intestine.
• Acute T. gondii infection led to downregulated CD73 expression, impairing adenosine production.
• Adenosine receptor activation limited immunopathology and gut dysbiosis, despite reduced ectonucleotidase activity.

Conclusions:

• Adenosinergic pathways involving CD39 and CD73 are critical for intestinal immune regulation.
• Therapeutic activation of adenosine receptors shows promise for controlling intestinal inflammation associated with impaired ectonucleotidase function.