Hannah Wood1,2, Animesh Acharjee3,4,5, Hayden Pearce1, Mohammed Nabil Quraishi6, Richard Powell1, Amanda Rossiter7, Andrew Beggs6, Andrew Ewer2,8, Paul Moss1, Gergely Toldi1,2. 1. Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK. 2. Department of Neonatology, Birmingham Women's and Children's NHS FT, Birmingham, UK. 3. Centre for Computational Biology, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK. 4. Institute of Translational Medicine, University Hospitals Birmingham NHS FT, Birmingham, UK. 5. NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham NHS FT, Birmingham, UK. 6. Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK. 7. Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK. 8. Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
Abstract
BACKGROUND: Breastfeeding is associated with long-term health benefits, such as a lower incidence of childhood infections, asthma, obesity and autoimmune disorders. However, little is known regarding how the maternal and neonatal immune systems interact after parturition when the neonate receives nutrition from maternal breast milk. METHODS: We undertook a comparative analysis of immune repertoire and function at birth and 3 weeks of age in a cohort of 38 term neonates born by caesarean section grouped according to feeding method (breast milk versus formula). We used flow cytometry to study the immune phenotype in neonatal and maternal blood samples and mixed lymphocyte reactions to establish the proliferation response of neonatal versus maternal lymphocytes and vice versa. The microbiome of neonatal stool samples was also investigated using 16S rRNA sequencing. RESULTS: We show that the proportion of regulatory T cells (Tregs) increases in this period and is nearly twofold higher in exclusively breastfed neonates compared with those who received formula milk only. Moreover, breastfed neonates show a specific and Treg-dependent reduction in proliferative T-cell responses to non-inherited maternal antigens (NIMA), associated with a reduction in inflammatory cytokine production. We also observed the enrichment of short chain fatty acid producing taxa (Veillonella and Gemella) in stool samples of exclusively breastfed neonates. CONCLUSIONS: These data indicate that exposure of the neonate to maternal cells through breastfeeding acts to drive the maturation of Tregs and 'tolerizes' the neonate towards NIMA.
BACKGROUND: Breastfeeding is associated with long-term health benefits, such as a lower incidence of childhood infections, asthma, obesity and autoimmune disorders. However, little is known regarding how the maternal and neonatal immune systems interact after parturition when the neonate receives nutrition from maternal breast milk. METHODS: We undertook a comparative analysis of immune repertoire and function at birth and 3 weeks of age in a cohort of 38 term neonates born by caesarean section grouped according to feeding method (breast milk versus formula). We used flow cytometry to study the immune phenotype in neonatal and maternal blood samples and mixed lymphocyte reactions to establish the proliferation response of neonatal versus maternal lymphocytes and vice versa. The microbiome of neonatal stool samples was also investigated using 16S rRNA sequencing. RESULTS: We show that the proportion of regulatory T cells (Tregs) increases in this period and is nearly twofold higher in exclusively breastfed neonates compared with those who received formula milk only. Moreover, breastfed neonates show a specific and Treg-dependent reduction in proliferative T-cell responses to non-inherited maternal antigens (NIMA), associated with a reduction in inflammatory cytokine production. We also observed the enrichment of short chain fatty acid producing taxa (Veillonella and Gemella) in stool samples of exclusively breastfed neonates. CONCLUSIONS: These data indicate that exposure of the neonate to maternal cells through breastfeeding acts to drive the maturation of Tregs and 'tolerizes' the neonate towards NIMA.
Authors: Enrique González-Madrid; Ma Andreina Rangel-Ramírez; María José Mendoza-León; Oscar Álvarez-Mardones; Pablo A González; Alexis M Kalergis; Ma Cecilia Opazo; Claudia A Riedel Journal: Int J Mol Sci Date: 2022-06-25 Impact factor: 6.208
Authors: Josephine Schlosser-Brandenburg; Friederike Ebner; Robert Klopfleisch; Anja A Kühl; Jürgen Zentek; Robert Pieper; Susanne Hartmann Journal: Front Immunol Date: 2021-08-16 Impact factor: 7.561