Journal article
Temporal Changes in Innate and Adaptive Immunity During Sepsis as Determined by ELISpot
Shock (Augusta, Ga.), Vol.62(2), pp.255-264
08/2024
DOI: 10.1097/SHK.0000000000002377
PMCID: PMC11348958
PMID: 38754032
Abstract
The inability to evaluate host immunity in a rapid quantitative manner in patients with sepsis has severely hampered development of novel immune therapies. The ELISpot assay is a functional bioassay that measures the number of cytokine-secreting cells and the relative amount of cytokine produced at the single-cell level. A key advantage of ELISpot is its excellent dynamic range enabling a more precise quantifiable assessment of host immunity. Herein, we tested the hypothesis that the ELISpot assay can detect dynamic changes in both innate and adaptive immunity as they often occur during sepsis. We also tested whether ELISpot could detect the effect of immune drug therapies to modulate innate and adaptive immunity.
Mice were made septic using sublethal cecal ligation and puncture (CLP). Blood and spleens were harvested serially and ex vivo IFN-γ and TNF-α production were compared by ELISpot and ELISA. The capability of ELISpot to detect changes in innate and adaptive immunity due to in vivo immune therapy with dexamethasone, IL-7, and arginine was also evaluated.
ELISpot confirmed a decreased innate and adaptive immunity responsiveness during sepsis progression. More importantly, ELISpot was also able to detect changes in adaptive and innate immunity in response to immune-modulatory reagents, for example dexamethasone, arginine, and IL-7 in a readily quantifiable manner, as predicted by the reagents known mechanisms of action. ELISpot and ELISA results tended to parallel one another although some differences were noted.
ELISpot offers a unique capability to assess the functional status of both adaptive and innate immunity over time. The results presented herein demonstrate that ELISpot can also be used to detect and follow the in vivo effects of drugs to ameliorate sepsis-induced immune dysfunction. This capability would be a major advance in guiding new immune therapies in sepsis.
Details
- Title: Subtitle
- Temporal Changes in Innate and Adaptive Immunity During Sepsis as Determined by ELISpot
- Creators
- Jacqueline Unsinger - Washington University in St. LouisDale Osborne - Washington University in St. LouisAndrew H Walton - Washington University in St. LouisEthan Han - Washington University in St. Louis School of MedicineLauren Sheets - Washington University in St. LouisMonty B Mazer - Case Western Reserve UniversityKenneth E Remy - Case Western Reserve UniversityThomas S Griffith - Minneapolis VA Health Care SystemMahil Rao - University of IowaVladimir P Badovinac - University of IowaScott C Brackenridge - Harborview Medical CenterIsaiah Turnbull - Washington University in St. LouisPhilip A Efron - University of FloridaLyle L Moldawer - University of FloridaCharles C Caldwell - University of Cincinnati Medical CenterRichard S Hotchkiss - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- Shock (Augusta, Ga.), Vol.62(2), pp.255-264
- DOI
- 10.1097/SHK.0000000000002377
- PMID
- 38754032
- PMCID
- PMC11348958
- eISSN
- 1540-0514
- Language
- English
- Electronic publication date
- 05/03/2024
- Date published
- 08/2024
- Academic Unit
- Critical Care; Stead Family Department of Pediatrics; Pathology
- Record Identifier
- 9984628222002771
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