Perinatal dysfunction of innate immunity in cystic fibrosis.

Summary

Using newborn CF pigs and preschool children with CF, the authors show a conserved perinatal innate immune defect characterized by increased immature myeloid infiltration, reduced CD16, and impaired phagocytosis/ROS generation before infection begins. These findings suggest CF lung disease is preceded by congenital innate immune dysfunction that may persist despite CFTR modulation.

Key Findings

• Newborn CF pigs exhibit increased monocyte infiltration and immature myeloid profiles in lungs before infection; neutrophil numbers unchanged.
• Decreased CD16 expression in myeloid cells is shared in CF pigs at birth and preschool children, correlating with reduced phagocytosis and ROS.
• Findings indicate a congenital, translationally conserved innate immune aberration in CF.

Clinical Implications

Supports early-life immune monitoring in CF, exploration of adjunct immunomodulation (e.g., enhancing phagocytosis/ROS or monocyte maturation), and refining infection-prevention strategies beginning in the perinatal period.

Limitations

• Human sample sizes and detailed demographics are not specified; human data appear cross-sectional.
• Causality and modifiability of innate defects under CFTR modulation were not directly tested.

Future Directions

Test whether early immunomodulation can normalize myeloid maturation/function in CF infants; delineate interactions with CFTR modulators; longitudinal birth cohorts to link innate defects to clinical outcomes.