S100-Alarmins Are Essential Pilots of Postnatal Innate Immune Adaptation

Abstract

The restricted capacity of newborn infants to mount inflammatory responses toward microbial challenges has traditionally been linked to the high risk of septic diseases during the neonatal period. In recent years, substantial evidence has been provided that this characteristic of the neonatal immune system is actually a meaningful physiologic state that is based on specific transiently active cellular and molecular mechanisms and required for a favorable course of postnatal immune adaptation. The identification of physiologically high amounts of S100-alarmins in neonates has been one of the crucial pieces in the puzzle that contributed to the change of concept. In this context, innate immune immaturity could be redefined and assigned to the epigenetic silence of adult-like cell-autonomous regulation at the beginning of life. S100-alarmins represent an alternative age-specific mechanism of immune regulation that protects neonates from hyperinflammatory immune responses. Here, we summarize how infants are provided with S100-alarmins and why these allow an uneventful clash between the innate immune system and the extrauterine world. The mode of action of S100-alarmins is highlighted including their tuning functions at multiple levels for establishing a state of homeostasis with the environment in the newborn individual.

Impacts of Enriched Human Milk Cells on Fecal Metabolome and Gut Microbiome of Premature Infants with Stage I Necrotizing Enterocolitis: A Pilot Study

“…[ 68 ] Studies have found that fecal calprotectin regulates the intestinal microbiota and immune system development in neonates. [ 69,70 ] In this study, we found that Enterococcus , a genus reported to be associated with active inflammation among IBD patients, [ 71,72 ] was positively correlated with calprotectin levels and the intensities of four sphingolipids. Moreover, Escherichia‐Shigella was negatively correlated with the intensities of six sphingolipids in the study, which may be associated with the bactericidal effect of sphingolipids in the gut.…”

Increased Expression of Anaphylatoxin C5a-Receptor-1 in Neutrophils and Natural Killer Cells of Preterm Infants

“…To our knowledge, this is the first study investigating gestational-age-dependent differences in the extra- and intracellular expression of C5aR1 and C5aR2 on peripheral blood leukocytes. The study is hypothesis-generating for further studies to explain the pro-inflammatory state that preterm infants are often confronted with [ 46 , 64 , 65 ]. The limitations of our study are the explorative, descriptive and single-center study design and relatively small cohort size.…”

Nutrition and Immunity in Perinatal Hypoxic-Ischemic Injury

“…Immune tolerance is important for three principal reasons: (a) to prevent rejection of the foetus, (b) to promote microbial colonisation after birth and (c) to prevent tissue damage from over-activation due to stress, injury and infection. Passive immunity from the mother is a critical component of immune protection both in utero and after birth (Figure 1, [6][7][8][9][10][11][12][13][14][15][16][17][18]). In these apparent quiescent phases, the immune system has the capacity to activate and respond to stressors that the foetus and neonate is exposed to in both specific and non-specific manners [6].…”