General microbial exposure establishes sustained myelopoiesis to provide enhanced innate resistance to infection 2709

Emma C. Kozurek; Cara Skon-Hegg; Caleb Y Kim; Tamara A. Kucaba; Jesse Warren Williams; Vladimir P. Badovinac; Thomas S Griffith

doi:10.1093/jimmun/vkaf283.597

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General microbial exposure establishes sustained myelopoiesis to provide enhanced innate resistance to infection 2709

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General microbial exposure establishes sustained myelopoiesis to provide enhanced innate resistance to infection 2709

Emma C. Kozurek, Cara Skon-Hegg, Caleb Y Kim, Tamara A. Kucaba, Jesse Warren Williams, Vladimir P. Badovinac and Thomas S Griffith

The Journal of immunology (1950), Vol.214(Supplement_1), vkaf283597

11/01/2025

DOI: 10.1093/jimmun/vkaf283.597

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Abstract

Abstract Description Bacterial infection of the bloodstream is a significant cause of morbidity and mortality worldwide. Studies with microbially experienced laboratory mice, produced by cohousing (CoH) with pet store mice, have provided insight on T cell biology not readily apparent in specific pathogen-free (SPF) mice. However, less is known about the impact of general microbial exposure on myeloid cell development and biology. Our data show the generalized microbial exposure experienced by CoH mice causes rapid (by d3), but sustained (d60), fundamental changes in early myeloid progenitor cells. CoH mice have more total bone marrow cells per femur, and an increased percentage and number of granulocyte/monocyte progenitors (GMP) within the lineage-cKit + (LK) subset, compared to SPF mice. Analysis of lineage-Sca1+cKit + (LSK) progenitors also showed a skewing toward MPP-granulocyte/monocyte (MPP-G/M) and away from MPP-lymphocyte (MPP-Ly) cells in CoH bone marrow. As such, CoH mice have an increase in CD115+ monocytes in the bone marrow and enhanced egress of Ly6ChiCD115+ monocytes from the bone marrow into the blood. CoH CD115+ monocytes have a higher mitochondrial content and metabolic activity, and show increased steady-state and LPS-induced TNF production. These features correlate with CoH mice being more resistant to systemic E. coli infection, and depletion of CD115+ monocytes abrogates this resistance. Thus, CoH mice reveal fresh perspectives on the innate immune response during bacteremia. Funding Sources Supported by NIH grants AI154527, GM140881, GM134880, AI165553 Topic Categories Hematopoiesis and Immune System Development (HEM)

Animals - Rodent Cells - Monocytes/Macrophages Stem Cells Infections - Bacterial Processes - Hematopoiesis

Details

Title: Subtitle: General microbial exposure establishes sustained myelopoiesis to provide enhanced innate resistance to infection 2709
Creators: Emma C. Kozurek
Cara Skon-Hegg - University of Minnesota
Caleb Y Kim
Tamara A. Kucaba - University of Minnesota
Jesse Warren Williams
Vladimir P. Badovinac
Thomas S Griffith - University of Minnesota
Resource Type: Abstract
Publication Details: The Journal of immunology (1950), Vol.214(Supplement_1), vkaf283597
DOI: 10.1093/jimmun/vkaf283.597
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: Oxford University Press
Grant note: NIH: AI154527, GM140881, GM134880, AI165553
Supported by NIH grants AI154527, GM140881, GM134880, AI165553
Alternative title: IMMUNOLOGY2025™ Abstracts
Language: English
Date published: 11/01/2025
Academic Unit: Pathology
Record Identifier: 9985034935202771

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