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Background: Immature immune systems predispose very low birth weight (VLBW) neonates to systemic infections in early life. Defective inflammasome function may increase a neonate's susceptibility to late-onset sepsis (LOS)., Methods: Blood samples were taken on the 5 th day of life (DOL) for all VLBW neonates (non-LOS and before-LOS groups; N.=76), and within 24 hours of sepsis onset (LOS group; N.=39). Monocyte (MO) subsets and intracellular interleukin-1β (IL-1β) expression were analyzed using flow cytometry. Inflammasome function, defined as level of IL-1β and interleukin-18 (IL-18) was measured with enzyme-linked immunosorbent assay. IRA B cells were reported as a fraction of all B cells., Results: Stimulation of classical MO in non-LOS cells demonstrated a higher expression of intracellular IL-1β in comparison to MO from before LOS group. Serum from the LOS group revealed a higher level of IL-18. Stimulation of mononuclear cultures from samples taken during LOS resulted in significantly increased supernatant level of IL-1β and IL-18 in comparison to samples taken on 5 th DOL. No changes in the levels of IRA B cells were detected with the onset of sepsis., Conclusions: We did not observe a difference in the functioning of the inflammasome within monocytes taken on 5 th DOL from premature VLBW neonates. Furthermore, there was no observable change in the IRA B cells of the septic and non-septic groups. The decreased expression of intracellular IL-1β within classical MO of the before-LOS group may be an independent risk factor for LOS development.

Background: Inflammasomes regulate activation of caspase-1, which cleaves and activates interleukin (IL)-1β and IL-18, the cytokines that trigger pro-inflammatory and antimicrobial responses. There is very little known about inflammasome function in the subsets of monocytes (MO) isolated from preterm neonates born extremely and very prematurely., Methods: A group of 76 very low birth weight patients without early-onset sepsis was divided into extremely preterm (<28 gestational week) or very preterm (28-32 gestational week) neonates. The first blood sample was collected on the 5th day of life (5th DOL) to analyse MO subsets as well as the intracellular IL-1β expression and supernatant concentration of IL-1β and IL-18. Secondary blood samples were collected within 24h of late-onset sepsis (LOS) development and analysed as above., Results: On the 5th DOL, the extremely preterm neonates were characterized by a significantly higher absolute count of MO, in particular in the classical and intermediate subsets, as compared to the very preterm group. The counts of the intermediate and non-classical MO subsets increased during LOS in all neonates. We did not observe significant differences in the intracellular IL-1β expression between the analysed groups. Furthermore, the levels of the analysed cytokines in the MO supernatants were comparable between the extremely and very preterm neonates on the 5th DOL. Finally, a higher level of IL-18 was observed in the supernatant of the extremely preterm group during LOS., Conclusions: During LOS, extremely preterm neonates excrete a higher level of IL-18 cytokines compared to very preterm neonates. Further studies are required to determine whether this observation is a result of a higher count of the circulating MO or is a true reflection of increased inflammasome function in this particular group of newborns., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Programmed death-1 (PD-1) receptor system represents a part of recently reported immunoregulatory pathway. PD-1 is an immune checkpoint molecule, which plays an important role in downregulating the immune system proinflammatory activity. Until recently, PD-1 expression was not established on immune cells of the preterm infants. The study objectives were to confirm expression of the PD-1 receptors on the monocytes isolated from very low birth weight newborns (VLBW), and to analyze their expression during the first week of life and late-onset sepsis. Peripheral blood mononuclear cells were isolated from 76 VLBW patients without early-onset sepsis on their 5th day of life (DOL). PD-1 expression was determined on the monocyte subsets (classical, intermediate, non-classical) by flow cytometry. In case of late-onset sepsis (LOS), the same analysis was performed. Our results demonstrated that on the 5th DOL, PD-1 receptors were present in all the monocyte subsets. Children, whose mothers had received antenatal steroids, presented higher absolute numbers of non-classical monocytes with PD-1 expression. Infants born extremely preterm who later developed LOS, initially showed a lower percentage of PD-1 receptor-positive intermediate monocytes in comparison to neonates born very preterm. During LOS, we observed a rise in the percentage of classical monocytes with PD-1 expression. In case of septic shock or fatal outcome, there was a higher percentage and absolute count of intermediate monocytes with PD-1 expression in comparison to children without these complications. In conclusion, monocytes from VLBW children express PD-1 receptors. Antenatal steroid administration seems to induce PD-1 receptor expression in the non-classical monocytes. PD-1 might play a role in immunosuppressive phase of sepsis in the prematurely born children with septic shock and fatal outcome.

The first report about the discovery of new, previously unknown immune cells named IRA B cells (innate response activator B cells) appeared in 2012. So far, their presence has been verified in both mice and humans. However, IRA B cells belong to the family of B lymphocytes and have a number of characteristics unique to this group of cells. IRA B cells are formed from activated B1a lymphocytes after their contact with a pathogen. B1a lymphocytes mainly reside within body cavities. Activated by the pathogen, they move on into secondary lymphoid organs (spleen, lymph nodes) where they differentiate into IRA B cells. IRA B cells are a rich source of granulocyte-macrophage colony stimulating factor (GM-CSF). GM-CSF can stimulate IRA B cells in an autocrine manner for the secretion of intracellular stocks of immunoglobulin M (IgM), which can facilitate pathogens' phagocytosis by neutrophils. GM-CSF also stimulates neutrophils into active phagocytosis. Rapid eradication of the pathogen can prevent the development of an excessive inflammatory response, which can be dangerous for the organism. Until now the involvement of IRA B lymphocytes in the pathogenesis of sepsis and pneumonia has been proven, as well as their role in the progression of atherosclerotic lesions in mice. There is research in progress on the possibility of increasing the number of IRA B cells, for example by intravenous supply of modified immunoglobulins. It is necessary to characterize human IRA B cells and to determine their role in the functioning of the immune system. [ABSTRACT FROM AUTHOR]