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Background Late-onset sepsis (LOS) with Staphylococcus epidermidis is common in preterm infants, but the immunological mechanisms underlying heightened susceptibility are poorly understood. Our aim is to characterize the ontogeny of cytokine responses to live S. epidermidis in preterm infants with and without subsequent Gram-positive LOS. Methods We conducted a prospective, observational cohort study of preterm infants (<30 weeks gestational age [GA]) with blood sampling on Days 1, 7, 14, 21, and 28 of life. Cytokine responses in peripheral whole blood stimulated with live S. epidermidis were analyzed by 11-plex immunoassay. Results Of 129 infants (mean GA, 26.2 weeks; mean birth weight, 887g), 23 (17.8%) had confirmed LOS with Gram-positive organisms and 15 (11.6%) had clinical sepsis, with median onsets at 13 and 15 days, respectively. Blood cytokine responses to an in vitro S. epidermidis challenge were similar between infected and uninfected infants on Day 1, but diverged thereafter. Infants with subsequent LOS displayed broadly reduced S. epidermidis– induced responses from Day 7 onwards, compared to those who did not develop LOS. This pattern was observed with chemokines (interleukin [IL]-8, monocyte chemotactic protein–1, and macrophage inflammatory protein–1α), pro-inflammatory cytokines (IL-1, IL-6, and tumor necrosis factor–α) and the regulatory cytokine IL-10. Conclusions Cytokine responses to a live S. epidermidis challenge are impaired in infants with LOS and precede the onset of clinical illness. Quantifying pathogen-specific cytokine responses at Day 7 may identify those high-risk preterm infants at the greatest risk of LOS, and prospective replication is warranted. [ABSTRACT FROM AUTHOR]

Review on preterm infant monocytes and how developmental immaturity of these cells may contribute to preterm infants' susceptibility to infections. The extreme vulnerability of preterm infants to invasive microbial infections has been attributed to "immature" innate immune defenses. Monocytes are important innate immune sentinel cells critical in the defense against infection in blood. They achieve this via diverse mechanisms that include pathogen recognition receptor‐ and inflammasome‐mediated detection of microbes, migration into infected tissues, and differentiation into Mϕs and dendritic cells, initiation of the inflammatory cascade by free radicals and cytokine/chemokine production, pathogen clearance by phagocytosis and intracellular killing, and the removal of apoptotic cells. Relatively little is known about these cells in preterm infants, especially about how their phenotype adapts to changes in the microbial environment during the immediate postnatal period. Overall, preterm monocytes exhibit attenuated proinflammatory cytokine responses following stimulation by whole bacterial or specific microbial components in vitro. These attenuated cytokine responses cannot be explained by a lack of intracellular signaling events downstream of pattern recognition receptors. This hyporesponsiveness also contrasts with mature, term‐like phagocytosis capabilities detectable even in the most premature infant. Finally, human data on the effects of fetal chorioamnionitis on monocyte biology are incomplete and inconsistent. In this review, we present an integrated view of human studies focused on monocyte functions in preterm infants. We discuss how a developmental immaturity of these cells may contribute to preterm infants' susceptibility to infections. [ABSTRACT FROM AUTHOR]