Natural Microbial Exposure from the Earliest Natural Time Point Enhances Immune Development by Expanding Immune Cell Progenitors and Mature Immune Cells

• DOI: 10.4049/jimmunol.2300061
• Publication Date: 2023-04-19T13:52:45Z
• Authors: Sarah Burger; Terran Stenger; Mark Pierson; Adhvaith Sridhar; Matthew A Huggins; Tamara A Kucaba; Thomas S Griffith; Sara E Hamilton; Nathaniel J Schuldt
• Keywords: Mice, Inbred C57BL; Mice; B-Lymphocytes; Bone Marrow; Stem Cells; Animals; Cytokines; Listeria monocytogenes

Abstract Microbial experience fundamentally shapes immunity, particularly during the perinatal period when immune system is underdeveloped, and novel microbial encounters are common. Most animal models raised in specific pathogen-free (SPF) conditions with relatively uniform communities. How SPF housing alter early-life development relative to natural exposure (NME) has not been thoroughly investigated. In this article, we compare SPF-raised mice born from immunologically experienced mothers microbially diverse environments. NME induced broad cell expansion, including naive cells, suggesting mechanisms besides activation-induced proliferation contribute increase numbers. We found also expanded progenitor populations bone marrow, enhances at earliest stages of differentiation. Multiple functions characteristically impaired infants were enhanced by NME, T memory Th1 polarization, B class switching Ab production, proinflammatory cytokine expression, bacterial clearance after Listeria monocytogenes challenge. Collectively, our studies reveal numerous impairments development.