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Uncovering the Dynamics of Immune Cell Populations in the First Week of Life: The Interplay of Neutrophils and Breastfeeding [methylation]

ABSTRACT: The first few days of life are characterized by rapid external and internal changes that require rapid host adaptations. Despite growing evidence of the impact of this period on an individual’s lifelong health trajectory, this period remains largely uncharted. To decipher key factors associated with changes in peripheral blood cell composition we conducted a stringently standardized, high-throughput immune phenotyping investigation on 796 newborns across diverse settings (The Gambia, West Africa and Papua New Guinea, Australasia) in the framework of a Human Immunology Project Consortium study. Samples were collected twice from each newborn during the first week of life and analyzed via high throughput flow cytometry with an unbiased automated gating algorithm to capture cell compositional changes at an unprecedented level of detail. We found that immune cell composition in peripheral blood changes along patterns highly conserved across populations and environments. Changes with age/day of life were most pronounced in the innate myeloid compartment. While there was minimal impact of sex, season of birth, mother’s age or origin (i.e., environmental and genetic background), breastfeeding and vaccination were strongly associated with increase in cell counts of peripheral blood neutrophils and monocytes. Our results may suggest a possible association of initiation of breastfeeding with changes in immune ontogeny, and thus possibly host immune-mediated protection from infection. These data begin to outline a specific window of opportunity for interventions that can deliberately direct immune ontogeny.

ORGANISM(S): Homo sapiens

PROVIDER: GSE273552 | GEO | 2024/08/05

REPOSITORIES: GEO

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Project description:Introduction: Early life is characterized by heightened susceptibility to infections and is recognized as a major determinant of the immune system development and the overall health for the entire human lifespan. However, our knowledge of the development of the neonatal immune system is incomplete, limiting the development of novel preventative and therapeutic strategies, especially in newborns. To gain insight into the early immune system development and plasma proteome ontogeny, the Expanded Program on Immunization Consortium (EPIC) led by Professor Ofer Levy MD at Boston Children’s Hospital, Harvard Medical School and Tobias R. Kollmann Telethon Kids Institute, Australia as part of the Human Immunological Project Consortium (HIPC), established two independent cohorts of plasma from healthy newborns born by vaginal delivery during the first week of life. Methods: Blood samples were collected from 30 newborns in The Gambia (Medical Research Council Unit, The Gambia) at the day of birth (day of life, DOL 0) and at one of the follow-up visits on DOL1, DOL3, or DOL7. A similar validation cohort was collected in Papua New Guinea (PNG) (Institute for Medical Research, Papua New Guinea, Australasian) from 19 newborns. The plasma proteome was characterized by LC-MS on a Q Exactive using the proven and published plasma proteomics platform developed in the Steen Laboratory, led by Dr Hanno Steen, Director of Proteomics at Boston Children’s Hospital, Harvard Medical School, employing only microliter of plasma prepared in a 96-well plate format. The data was analyzed with MaxQuant. Results: We characterized 385 blood-plasma proteins. Utilizing the paired study design, we identified consistent changes related to ontogeny and cellular growth pathways in the blood-plasma proteome. Conclusion: This dataset allows for studying the early ontogeny of the plasma proteome, and in extension the early immune system development, in two independent healthy cohorts. Characterization of the plasma proteome may provide novel insight into new approaches to prevent, detect, and treat infectious diseases. Acknowledgements: We would like to thank all the participating families and all past and current members of the EPIC-HIPC, and the Steen Laboratory, without whom this study would not be possible. A special recognition goes to the teams who established the unique cohorts in The Gambia, by Professor Beate Kampmann and Dr Olubukola T. Idoko at The Gambia at the London School of Hygiene and Tropical Medicine, The Gambia, and in PNG, by Anita H.J. van der Biggelaar and William S. Pomat at Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia Perth, Australia.

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Uncovering the Dynamics of Immune Cell Populations in the First Week of Life: The Interplay of Neutrophils and Breastfeeding [methylation]

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