Gut Microbes Trigger Calprotectin to Protect Newborns from Infection

Newborns' immune systems differ significantly from those of adults, with the mechanisms enabling early-life immunity still largely unknown. Infant vulnerability to infection is a major concern, making understanding these early immune mechanisms crucial. A new study in Science Translational Medicine reveals that calprotectin, an antimicrobial protein abundant in newborn mice guts, plays a key role in protecting against infection.

Calprotectin is expressed by intestinal epithelial cells in response to the colonization of the gut by commensal bacteria. Healthy newborn mice exhibit high concentrations of calprotectin, which is initiated by the initial exposure to these bacteria. Mice with impaired calprotectin expression or poor microbiota colonization are more susceptible to sepsis and death following infection.

However, administering calprotectin to microbiota-depleted pups prevents infection. The source of calprotectin in the neonatal intestine is attributed to commensal-induced S100A9 expression by intestinal epithelial cells. The study highlights specific mechanisms that enable early-life immunity against dangerous pathogens like Staphylococcus aureus, Listeria monocytogenes, and Streptococcus pneumoniae during a critical period when newborns have limited other immune defenses.

These findings suggest that microbiota-epithelial dynamics at birth can program early-life immunity, potentially paving the way for probiotic approaches targeting epithelial cells to prevent neonatal sepsis. The presence of calprotectin in human newborns' guts less than two days old, but not in seven-year-old infants, suggests a similar early-life immune mechanism may exist in humans.