Basophil-Derived IL-4 and IL-13 Protect Intestinal Barrier Integrity and Control Bacterial Translocation during...

Area of Science:

• Immunology
• Parasitology
• Gastroenterology

Background:

• Basophils are key regulators of malaria phenotypes, including intestinal inflammation and parasite transmission.
• Activated basophils are primary sources of interleukin-4 (IL-4) and interleukin-13 (IL-13), critical regulatory cytokines.

Purpose of the Study:

• To investigate the role of basophil-derived IL-4 and IL-13 in regulating malaria-associated phenotypes.
• To determine the contribution of these cytokines to intestinal barrier integrity and parasite transmission.

Main Methods:

• Generation of mice with basophils depleted of IL-4 and IL-13 (baso IL-4/IL-13 (-)) using mcpt8-Cre and Il4/Il13fl/fl crosses.
• Infection of these mice and control littermates (baso IL-4/IL-13 (+)) with Plasmodium yoelii yoelii 17XNL.
• Assessment of intestinal mastocytosis, permeability, bacterial translocation (16S levels), and parasite transmission.

Main Results:

• Conditional deletion of IL-4/IL-13 in basophils led to ileal mastocytosis, mast cell activation, and increased intestinal permeability.
• Increased bacterial 16S levels in blood were observed in baso IL-4/IL-13 (-) mice, indicating impaired control of bacterial translocation.
• Basophil-derived IL-4 and IL-13 did not affect neutrophil activation, parasitemia, or transmission to Anopheles stephensi.

Conclusions:

• Basophil-derived IL-4 and IL-13 are essential for protecting intestinal barrier integrity during Plasmodium yoelii infection.
• These cytokines regulate mast cell activation and prevent infection-induced intestinal damage and bacteremia.
• The findings suggest a role for basophil IL-4/IL-13 in modulating eosinophil, macrophage, and Th17-mediated inflammation.