Neonates, particularly those born prematurely, are exquisitely vulnerable to life-threatening infections. This increased susceptibility to infection is maintained into childhood. Despite the considerable human and economic cost of infection-related neonatal morbidity and mortality, the mechanisms underlying this heightened susceptibility are only partly understood. It is increasingly recognised that innate immune responses are key to the protection against infection early in life, and emerging data suggest that such responses are deficient in the newborn and especially in preterm infants. Here we review the current understanding of the maturation of the innate immune response in human neonates highlighting the clinical relevance and possible avenues for therapeutic intervention.

Neonates, especially those born preterm, are at increased risk of sepsis and adverse long-term effects associated with infection-related inflammation. Distinct neonatal immune responses and dysregulated inflammation are central to this unique susceptibility. The traditional separation of sepsis into an initial hyper-inflammatory response followed by hypo-inflammation is continually under review with new developments in this area of research. There is evidence to support the association of mortality in the early acute phase of sepsis with an overwhelming hyper-inflammatory immune response. Emerging evidence from adults suggests that hypo- and hyper-inflammation can occur during any phase of sepsis and that sepsis-immunosuppression is associated with increased mortality, morbidity, and risk to subsequent infection. In adults, sepsis-induced immunosuppression (SII) is characterised by alterations of innate and adaptive immune responses, including, but not limited to, a prominent bias toward anti-inflammatory cytokine secretion, diminished antigen presentation to T cells, and reduced activation and proliferation of T cells. It is unclear if sepsis-immunosuppression also plays a role in the adverse outcomes associated with neonatal sepsis. This review will focus on exploring if key characteristics associated with SII in adults are observed in neonates with sepsis.

Coagulase-negative staphylococci have emerged as the most common nosocomial pathogen in neonatal intensive care units worldwide. Our understanding of the interactions between coagulase-negative staphylococci and the immune system is incomplete, especially in the newborn. This review summarizes current knowledge on the human immune response to coagulase-negative staphylococci, with particular emphasis on the neonatal innate immune system. There are very limited data on innate immune responses to coagulase-negative staphylococci in neonates. Levels of serum proteins, including transplacental anti-coagulase-negative staphylococci immunoglobulin and complement, correlate with gestational age, and this relative deficiency in preterm infants contributes to their suboptimal opsonization and impaired bacterial killing of coagulase-negative staphylococci. In adults, coagulase-negative staphylococci elicit significant cytokine responses in vitro, which are probably partly mediated by Toll-like receptors, including Toll-like receptor type 2, but these pathways have not been characterized in the high-risk neonatal population. The susceptibility of human preterm neonates to coagulase-negative staphylococci relates partly to the immaturity of the neonatal immune response. Strategies to reduce the burden of coagulase-negative staphylococci infections require a thorough understanding of host-pathogen interactions, particularly the engagement of coagulase-negative staphylococci by the neonatal innate immune system.