Sepsis leads to lasting changes in phenotype and function of naïve CD8 T cells

Roger R. Berton; Patrick W. McGonagil; Isaac J. Jensen; Tiffany K. Ybarra; Gail A. Bishop; John T. Harty; Thomas S. Griffith; Vladimir P. Badovinac

doi:10.1371/journal.ppat.1011720

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Sepsis leads to lasting changes in phenotype and function of naïve CD8 T cells

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Sepsis leads to lasting changes in phenotype and function of naïve CD8 T cells

Roger R. Berton, Patrick W. McGonagil, Isaac J. Jensen, Tiffany K. Ybarra, Gail A. Bishop, John T. Harty, Thomas S. Griffith and Vladimir P. Badovinac

PLoS pathogens, Vol.19(10), e1011720

10/2023

DOI: 10.1371/journal.ppat.1011720

PMCID: PMC10597476

PMID: 37824591

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Abstract

Sepsis, an amplified immune response to systemic infection, is characterized by a transient cytokine storm followed by chronic immune dysfunction. Consequently, sepsis survivors are highly susceptible to newly introduced infections, suggesting sepsis can influence the function and composition of the naïve CD8 T cell pool and resulting pathogen-induced primary CD8 T cell responses. Here, we explored the extent to which sepsis induces phenotypic and functional changes within the naïve CD8 T cell pool. To interrogate this, the cecal ligation and puncture (CLP) mouse model of polymicrobial sepsis was used. In normal, non-septic mice, we show type-I interferon (IFN I)-mediated signaling plays an important role in driving the phenotypic and functional heterogeneity in the naïve CD8 T cell compartment leading to increased representation of Ly6C + naïve CD8 T cells. In response to viral infection after sepsis resolution, naïve Ly6C + CD8 T cells generated more primary effector and memory CD8 T cells with slower conversion to a central memory CD8 T cell phenotype (Tcm) than Ly6C - naïve CD8 T cells. Importantly, as a potent inducer of cytokine storm and IFN I production, sepsis leads to increased representation of Ly6C + naïve CD8 T cells that maintained their heightened ability to respond (i.e., effector and memory CD8 T cell accumulation and cytokine production) to primary LCMV infection. Lastly, longitudinal analyses of peripheral blood samples obtained from septic patients revealed profound changes in CD8 T cell subset composition and frequency compared to healthy controls. Thus, sepsis has the capacity to alter the composition of naïve CD8 T cells, directly influencing primary CD8 T cell responses to newly introduced infections.

Details

Title: Subtitle: Sepsis leads to lasting changes in phenotype and function of naïve CD8 T cells
Creators: Roger R. Berton - University of Iowa
Patrick W. McGonagil - University of Iowa
Isaac J. Jensen - Columbia University Irving Medical Center
Tiffany K. Ybarra - University of Iowa
Gail A. Bishop - University of Iowa
John T. Harty - University of Iowa
Thomas S. Griffith - University of Minnesota
Vladimir P. Badovinac - University of Iowa
Contributors: Matthew A Mulvey (Editor)
Resource Type: Journal article
Publication Details: PLoS pathogens, Vol.19(10), e1011720
DOI: 10.1371/journal.ppat.1011720
PMID: 37824591
PMCID: PMC10597476
NLM abbreviation: PLoS Pathog
ISSN: 1553-7374
eISSN: 1553-7374
Grant note: name: NIH/NIGMS, award: GM134880; name: NIH/NIAID, award: AI114543; name: NIH/NIAID, award: AI007485; name: NIH/NIAID, award: AI007511; name: NIH/NIAID, award: AI042767; name: NIH/NIAID, award: AI167847; name: NIH/NIGMS, award: GM140881; name: NCI, award: CA086862
Language: English
Electronic publication date: 10/12/2023
Date published: 10/2023
Academic Unit: Microbiology and Immunology; President; Pathology; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9984479556102771

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