Investigating the Role of Maternal Microbiota and Antibodies in Development of the Neonatal Immune System
Date
2023-05-02
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Abstract
Microbial colonization in early life plays a critical role in the development and education of the host’s immune system. However, the precise mechanisms underlying microbial-immune interactions during the early life period are still under investigated. Postnatal colonization of the body with microbes was assumed to be the main stimulus for neonatal immune development. However, our group previously demonstrated that the maternal microbiota during gestation shapes the immune system of the offspring, both in utero and postnatally. This thesis aims to examine the underlying mechanisms by which the maternal microbiota drives neonatal immune development and the functional consequence of the maternal microbiota on offspring resistance to systemic infection. To disassociate the effects of the maternal microbiota from microbial signals coming from colonization after birth, a model of ‘gestational-only colonization’ was utilized. Firstly, the neonatal Fc receptor (FcRn) was found to be required for gestational-only colonization to induce ILC3 populations in the neonatal gut. Mechanistically, this suggests that the FcRn is necessary for transportation of maternal IgG-bound microbial products and metabolites to the offspring. Secondly, transfer of maternal anti-E. coli IgG induced ILC3 populations in the neonate, even when it was associated with products and metabolites generated by another bacterial species. This suggests that bacterial molecules may bind IgG in a non-specific manner and that this is sufficient to transfer the associated molecules to induce offspring immune cell changes. Lastly, we found gestational-only colonization led to reduced bacterial load in multiple offspring systemic organs after intravenous challenge with the pathogen S. aureus. Despite this, gestational-only colonization was not sufficient to protect the neonate from bacterial sepsis. Overall, this thesis revealed how maternal microbial products and metabolites are handled at the maternal-offspring interface in early life to educate the neonatal immune system and impact health outcomes in systemic infection.
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Keywords
Neonate, Maternal microbiome, Immune system, Early-life development, Innate lymphoid cells, Intestinal monomuclear cells
Citation
Czyz, S. (2023). Investigating the role of maternal microbiota and antibodies in development of the neonatal immune system (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.