Abstract
Infection and sepsis remain among the leading causes of neonatal mortality. The susceptibility of newborns to infection can be attributed to their immature immune system. Regarding immune response, monocytes represent a numerically minor population of leukocytes. However, they contribute to a variety of immunological demands, such as continuous replenishment of resident macrophages under non-infectious conditions and migration to inflamed sites where they neutralize pathogens and secrete cytokines. Further functions include the presentation of antigens and T-cell activation. Cytokines coordinate host responses to bacterial and viral infections and orchestrate ongoing physiological signaling between cells of non-immune tissues. A critical event is the skewing of the cytokine repertoire to achieve a resolution of infection. In this regard, monocytes may hold a key position as deciders in addition to their phagocytic activity, securing the extinction of pathogens to prevent broader organ damage by toxins and pro-inflammatory reactions. Neonatal monocytes undergo various regulatory and metabolic changes. Thus, they are thought to be vulnerable in anticipating pro-inflammatory conditions and cause severe progressions which increase the risk of developing sepsis. Furthermore, clinical studies have shown that exposure to inflammation puts neonates at a high risk for adverse pulmonary, immunological and other organ developments, which may result in multiorgan disease. This review discusses significant functions and impairments of neonatal monocytes that are decisive for the outcome of bacterial infections.
Highlights
This review focuses on the armamentarium of neonatal monocytes and their potential to orchestrate an adequate antibacterial immune response during sepsis as think tanks or workhorses
While few studies show lower phagocytic ability [23], we and others have shown that infection with green fluorescent protein (GFP)-labeled bacteria revealed no difference between peripheral blood monocytes from adults (PBMOs) and cord blood derived monocytes (CBMO) with regard to phagocytic capacity, phagocytic indices, degradation activity and reactive oxygen species (ROS) production [18,23,24,25]
Neonatal monocytes displayed a compromised ability to activate T-cells, whereas IL-10 production was enhanced, which could, again, correlate with the high proportion of intermediate monocytes [58,59]. These results suggest that neonatal monocyte subtypes are skewed towards an immunosuppressive and anti-inflammatory phenotype which could protect from hyperinflammation during early microbial colonization and lead to lowered anti-bacterial protective capacity in case of disease
Summary
The detection of pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs) is the starting point of inflammation [9]. Invading pathogens or components such as lipopolysaccharides (LPS) and lipoteichoic acid (LTA) cause the production of pro-inflammatory cytokines via the activation of PRRs, such as Toll-like receptors (TLRs) expressed by monocytes [10]. Surface expression levels of TLR2, mainly involved in the detection of Gram-positive bacteria, showed no significant difference compared to adult monocytes [16], while others have reported reduced TLR2 expression on neonatal monocytes [17]. This results in deficiencies in innate immunity-associated inflammatory cytokine response, which has been widely demonstrated [18]. It can be assumed that the capacity of monocytes to detect pathogens is an important function in sepsis; altered signalling pathways in neonatal monocytes have yet to be elucidated
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