INTRODUCTION: Probiotic administration seems to be a rational approach to promote maturation of the neonatal immune system. Mutual interaction of the microbiota with the host immune system is critical for the setting of appropriate immune responses including a tolerogenic one and thevmaintenance of homeostasis. On the other hand, our knowledge on the modes of actions of probiotics is still scarce. METHODS: In our study, probiotic strain Escherichia coli O83:K24:H31 (EcO83) was administered to neonates of allergic mothers (AMs; neonates with increased risk for allergy development) within 48 h after the delivery, and the impact of this early postnatal supplementation on allergy incidence and selected immune markers has been analyzed 10 years after the primary EcO83 administration. RESULTS: We have observed decreased allergy incidence in 10-year-old children supplemented with EcO83 (13 of 52 children were allergic) in comparison with non-supplemented children of AMs (16 of 42 children were allergic). The early postnatal EcO83 supplementation appeared to limit the allergy in the high-risk group (children of AMs) compared to that in the low-risk group (children of healthy mothers). Dendritic cells (DCs) in the peripheral blood of EcO83-supplemented children do not differ significantly in cell surface presence of CD83. The immunomodulatory capacity of EcO83 on DCs was tested in vitro as well. Both directly isolated myeloid and in vitro monocyte-derived DCs from cord blood increased CD83 expression together with interleukin (IL)-10 secretion after EcO83 stimulation. The effect of early postnatal EcO83 supplementation on the microbiota composition of 10-year-old children was characterized by next-generation sequencing, and we have not observed significant changes in the microbiota composition of EcO83-supplemented and non-supplemented children at the age of 10 years. CONCLUSIONS: Early postnatal EcO83 supplementation appears to lower allergy incidence in children of AMs. It seems that the beneficial effect of EcO83 is mediated via modulation of DC functional capacities without impacting the microbiota composition. Larger-scale studies will be necessary to confirm these preliminary findings.

• Klíčová slova
• CD83, Escherichia coli O83:K24:H31, IL-10, allergy, cord blood, dendritic cell, flow cytometry, probiotic,
• MeSH
• alergie * epidemiologie   prevence a kontrola   MeSH
• dendritické buňky MeSH
• dítě MeSH
• Escherichia coli fyziologie   MeSH
• incidence MeSH
• lidé MeSH
• mikrobiota * MeSH
• monocyty MeSH
• novorozenec MeSH
• probiotika * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Understanding the early events involved in the induction of immune tolerance to harmless environmental antigens and microbiota compounds could reveal potential targets for allergic disease therapy or prevention. Regulatory T cells (Treg), particularly induced Treg (iTreg), are crucial for the induction and maintenance of tolerance against environmental antigens including allergens. A decrease in the number and/or function of Treg or iTreg could represent an early predictor of allergy development. We analyzed proportional and functional properties of Treg in the cord blood of children of allergic mothers (neonates at high risk of allergy development) and healthy mothers (neonates with relatively low risk of allergy development). We observed a higher number of induced Treg in the cord blood of females compared to males, suggesting an impaired capacity of male immunity to set up tolerance to allergens, which could contribute to the higher incidence of allergy observed in male infants. The decreased proportion of iTreg in cord blood compared with maternal peripheral blood documents the general immaturity of the neonatal immune system. We observed a positive correlation in the demethylation of the Treg-specific demethylated region (TSDR) and the proportion of Treg in cord blood. Our data suggest that immaturity of the neonatal immune system is more severe in males, predisposing them to increased risk of allergy development.

• Klíčová slova
• Helios, TSDR, allergy, cord blood, epigenetics, flow cytometry, induced Treg, natural Treg, regulatory T cells,
• Publikační typ
• časopisecké články MeSH

Allergic diseases represent some of the most common immunological disorders with high clinical and economic impact. Despite intensive research, there are still few universally accepted and reliable biomarkers capable of predicting their development at an early age. There is therefore a pressing need for identification of potential predictive factors and validation of their prognostic value by correlating them with allergy development. Dysbalance of the branches of immune response, most often excessive Th2 polarization, is the principal cause of allergic diseases. Regulatory T cells (Treg) are a crucial population for the timely establishment of physiological immune polarization and induction and maintenance of tolerance against environmental antigens. This makes them a potentially promising candidate for an early marker predicting allergy development. In our study, we analysed samples of cord blood of children of allergic mothers and children of healthy mothers by flow cytometry and retrospectively correlated the data with clinical allergy status of the children at the age of 6 to 10 years. Studied parameters included cord blood Treg population proportions and functional properties - intracellular presence of IL-10 and TGF-b, MFI of FoxP3. We observed higher percentage of Tregs in cord blood of children who did not develop allergy compared with allergic children. Further, we found higher numbers of IL-10+ Tregs in cord blood of healthy children of healthy mothers than in cord blood of children of allergic mothers and decreased TGF-b+ cord blood Tregs in the group of allergic children of allergic mothers compared to all other groups.

• Klíčová slova
• IL-10, TGF-b, Treg, allergy, cord blood, regulatory T cells,
• Publikační typ
• časopisecké články MeSH

Continuous increasing incidence of allergic diseases is calling for identifying early prognostic markers pointing to increased risk of allergy development and establishing protocols for preventive strategies limiting allergy development in predisposed individuals. It is important to better understand the critical events occurring in early postnatal life, especially the interaction of a newborn with microbial compounds important for the maturation of the neonatal immune system and setting immunoregulatory responses as well. Dendritic cells (DC) together with the cytokine microenvironment play an important role in priming of immune responses. The capacity of monocyte-derived DC (moDC) from cord blood of children of healthy and allergic mothers to respond to microbial antigens (Escherichia coli O86 (EcO86) and delipidated Bacillus firmus (DBF)) was tested by flow cytometry and quantitative real-time PCR. Both EcO86 and DBF were able to promote maturation of moDC, but moDC of children of allergic mothers expressed higher levels of activation markers CD80 and CD83. Increased gene expression of IL-6 and lower expression of indol-amine 2,3 dioxygenase were observed in moDC of neonates of allergic mothers, in comparison to healthy ones. A higher gene expression and an increased presence of activation markers on moDC of newborns of allergic mothers indicate a generally higher reactivity of these cells, possibly enabling easier development of inappropriate immune response after an allergen encounter.

• MeSH
• alergie krev   diagnóza   MeSH
• antigeny bakteriální imunologie   MeSH
• antigeny povrchové genetika   metabolismus   MeSH
• biologické markery metabolismus   MeSH
• cytokiny genetika   metabolismus   MeSH
• dendritické buňky imunologie   MeSH
• fetální krev MeSH
• kultivované buňky MeSH
• lidé MeSH
• matky MeSH
• monocyty imunologie   MeSH
• novorozenec MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny bakteriální MeSH
• antigeny povrchové MeSH
• biologické markery MeSH
• cytokiny MeSH