CD115+ monocytes protect microbially experienced mice against E. coli-induced sepsis

Matthew D. Martin; Cara Skon-Hegg; Caleb Y. Kim; Julie Xu; Tamara A. Kucaba; Whitney Swanson; Mark J. Pierson; Jesse W. Williams; Vladimir P. Badovinac; Steven S. Shen; Molly A. Ingersoll; Thomas S. Griffith

Cell Reports (Nov 2023)

CD115+ monocytes protect microbially experienced mice against E. coli-induced sepsis

Matthew D. Martin,
Cara Skon-Hegg,
Caleb Y. Kim,
Julie Xu,
Tamara A. Kucaba,
Whitney Swanson,
Mark J. Pierson,
Jesse W. Williams,
Vladimir P. Badovinac,
Steven S. Shen,
Molly A. Ingersoll,
Thomas S. Griffith

Affiliations

Matthew D. Martin: Department of Urology, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
Cara Skon-Hegg: Department of Urology, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
Caleb Y. Kim: Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota, Minneapolis, MN 55455, USA
Julie Xu: Department of Urology, University of Minnesota, Minneapolis, MN 55455, USA
Tamara A. Kucaba: Department of Urology, University of Minnesota, Minneapolis, MN 55455, USA
Whitney Swanson: Department of Urology, University of Minnesota, Minneapolis, MN 55455, USA
Mark J. Pierson: Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
Jesse W. Williams: Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN 55455, USA
Vladimir P. Badovinac: Department of Pathology, University of Iowa, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA
Steven S. Shen: Institute for Health Informatics, University of Minnesota, Minneapolis, MN 55455, USA
Molly A. Ingersoll: Université Paris Cité, Institut Cochin, INSERM U1016, CNRS UMR 8104, 75014 Paris, France; Mucosal Inflammation and Immunity, Department of Immunology, Institut Pasteur, Inserm U1223, 75015 Paris, France
Thomas S. Griffith: Department of Urology, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Minneapolis VA Health Care System, Minneapolis, MN 55417, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 11
p. 113345

Abstract

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Summary: Uropathogenic E. coli (UPEC) is a primary organism responsible for urinary tract infections and a common cause of sepsis. Microbially experienced laboratory mice, generated by cohousing with pet store mice, exhibit increased morbidity and mortality to polymicrobial sepsis or lipopolysaccharide challenge. By contrast, cohoused mice display significant resistance, compared with specific pathogen-free mice, to a monomicrobial sepsis model using UPEC. CD115+ monocytes mediate protection in the cohoused mice, as depletion of these cells leads to increased mortality and UPEC pathogen burden. Further study of the cohoused mice reveals increased TNF-α production by monocytes, a skewing toward Ly6ChiCD115+ “classical” monocytes, and enhanced egress of Ly6ChiCD115+ monocytes from the bone marrow. Analysis of cohoused bone marrow also finds increased frequency and number of myeloid multipotent progenitor cells. These results show that a history of microbial exposure impacts innate immunity in mice, which can have important implications for the preclinical study of sepsis.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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