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Published on: February 19, 2013
CD115+ monocytes protect microbially experienced mice against E. coli-induced sepsis
Matthew D Martin1,2,3, Cara Skon-Hegg1,2,3, Caleb Y Kim2,4
1Department of Urology, University of Minnesota, Minneapolis, MN 55455, USA.
Abstract:
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.
Insights
Microbial exposure enhances innate immunity in mice, protecting against urinary tract infections caused by E. coli. This involves specific monocyte responses, crucial for understanding sepsis preclinical models.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Uropathogenic E. coli (UPEC) is a major cause of urinary tract infections and sepsis.
- Microbial experience in mice influences sepsis outcomes.
Purpose of the Study:
- To investigate the impact of microbial experience on innate immunity against UPEC sepsis.
- To identify immune mechanisms conferring protection in microbially experienced mice.
Main Methods:
- Cohousing laboratory mice with pet store mice to induce microbial experience.
- Monomicrobial sepsis model using UPEC.
- Flow cytometry to analyze monocyte populations (CD115+, Ly6Chi).
- Depletion studies of CD115+ monocytes.
Main Results:
- Cohoused mice showed resistance to UPEC sepsis compared to specific pathogen-free mice.
- CD115+ monocytes were critical for protection, with their depletion increasing mortality.
- Increased TNF-α production, a skewing towards Ly6ChiCD115+ monocytes, and enhanced monocyte egress from bone marrow were observed.
- Increased myeloid multipotent progenitor cells in cohoused mice bone marrow.
Conclusions:
- Prior microbial exposure primes innate immunity, conferring resistance to UPEC sepsis in mice.
- CD115+ monocytes play a key protective role.
- These findings highlight the importance of microbial history in preclinical sepsis research.
