Ascorbate and TET2 couple balanced hematopoiesis to disease tolerance

Ascorbate-TET signaling in myeloid progenitors limits excessive myelopoiesis and is essential for surviving malaria in mice.

• Why it matters: Infection-driven myelopoiesis can reduce other blood lineages, but whether restoring balance improves infection outcomes and disease tolerance was unclear.
• What they did: Hematopoietic-specific ascorbate depletion increased myelopoiesis, and ascorbate effects depended on TET2/TET3 activity; combined ascorbate and TET2 depletion strongly skewed hematopoiesis toward myeloid cells and impaired erythropoiesis.
• The result: In mice infected with Plasmodium parasites, loss of ascorbate and TET2 allowed pathogen clearance but caused exacerbated myeloid expansion, impaired erythroid responses, anemia, tissue damage, and death—indicating reduced disease tolerance.

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