Journal article
Immune unresponsiveness to secondary heterologous bacterial infection after sepsis induction is TRAIL-dependent
The Journal of immunology (1950), Vol.187(5), pp.2148-2154
09/01/2011
DOI: 10.4049/jimmunol.1101180
PMCID: PMC3159846
PMID: 21788440
Abstract
Sepsis is the leading cause of death in most ICU’s, and patients who survive the hyper-inflammation that develops early during sepsis later display severely compromised immunity. Not only is there apoptosis of lymphoid and myeloid cells during sepsis that depletes these critical cellular components of the immune system, but the remaining immune cells also show decreased function. Using a cecal-ligation and puncture (CLP) model to induce intra-abdominal polymicrobial peritonitis, we recently established a link between the apoptotic cells generated during sepsis and induction of sepsis-induced suppression of delayed-type hypersensitivity. The present study extends this earlier work to include a secondary heterologous bacterial infection (OVA-expressing
Listeria monocytogenes
; LM-OVA) subsequent to sepsis initiation to investigate sepsis-induced alterations in the control of this secondary infection and the associated naïve Ag-specific CD8 T cell response. We found that CLP-treated WT mice had a reduced ability to control the LM-OVA infection, which was paralleled by suppressed T cell responses, versus sham-treated WT mice. In contrast, CLP-treated
Trail
−/−
and
Dr5
−/−
mice were better able to control the secondary bacterial infection and the Ag-specific CD8 T cell response was similar to that seen in sham-treated mice. Importantly, administration of a blocking anti-TRAIL mAb to CLP-treated WT mice was able to restore the ability to control the LM-OVA infection and generate Ag-specific CD8 T cell responses like those seen in sham-treated mice. These data further implicate TRAIL-dependent immune suppression during sepsis, and suggest TRAIL neutralization may be a potential therapeutic target to restore cellular immunity in septic patients.
Details
- Title: Subtitle
- Immune unresponsiveness to secondary heterologous bacterial infection after sepsis induction is TRAIL-dependent
- Creators
- Prajwal Gurung - Department of Urology, University of Iowa, Iowa City, IA 52242Deepa Rai - Department of Pathology, University of Iowa, Iowa City, IA 52242Stephanie A Condotta - Department of Pathology, University of Iowa, Iowa City, IA 52242Jeffrey C Babcock - University of Iowa Interdisciplinary Summer Undergraduate Research Program, University of Iowa, Iowa City, IA 52242Vladimir P Badovinac - Department of Pathology, University of Iowa, Iowa City, IA 52242Thomas S Griffith - Department of Urology, University of Iowa, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.187(5), pp.2148-2154
- DOI
- 10.4049/jimmunol.1101180
- PMID
- 21788440
- PMCID
- PMC3159846
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- R01 AI083286-03 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
- Language
- English
- Date published
- 09/01/2011
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Pathology; Internal Medicine
- Record Identifier
- 9984047851502771
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