Longitudinal analysis of mucosa-associated invariant T cells in sepsis reveals their early numerical decline with prognostic implications and a progressive loss of antimicrobial functions.
Joshua ChoiCrystal L SchmerkTina S MelePatrick T RudakChristine M WardellGansen DengFarzan R PavriKyoungok KimGediminas CepinskasWenqing HeS M Mansour HaeryfarPublished in: Immunology and cell biology (2023)
Sepsis-elicited immunosuppression elevates the risk of secondary infections. We used a clinically relevant mouse model and serial peripheral blood samples from patients to assess the antimicrobial activities of mucosa-associated invariant T (MAIT) cells in sepsis. Hepatic and splenic MAIT cells from B6-MAIT CAST mice displayed increased CD69 expression and a robust interferon-γ (IFNγ) production capacity shortly after sublethal cecal ligation and puncture, but not at a late timepoint. Peripheral blood MAIT cell frequencies were reduced in septic patients at the time of intensive care unit (ICU) admission, and more dramatically so among nonsurvivors, suggesting the predictive usefulness of early MAIT cell enumeration. In addition, at ICU admission, MAIT cells from sepsis survivors launched stronger IFNγ responses to several bacterial species compared with those from patients who subsequently died of sepsis. Of note, while low human leukocyte antigen (HLA)-DR + monocyte frequencies, widely regarded as a surrogate indicator of sepsis-induced immunosuppression, were gradually corrected, the numerical insufficiency of MAIT cells was not resolved over time, and their CD69 expression continued to decline. MAIT cell responses to bacterial pathogens, a major histocompatibility complex-related protein 1 (MR1) ligand, and interleukin (IL)-12 and IL-18 were also progressively lost during sepsis and did not recover by the time of ICU/hospital discharge. We propose that MAIT cell dysfunctions contribute to post-sepsis immunosuppression.
Keyphrases
- intensive care unit
- acute kidney injury
- septic shock
- peripheral blood
- mechanical ventilation
- single cell
- cell therapy
- dendritic cells
- endothelial cells
- induced apoptosis
- mouse model
- emergency department
- poor prognosis
- multiple sclerosis
- stem cells
- end stage renal disease
- staphylococcus aureus
- mesenchymal stem cells
- immune response
- type diabetes
- ejection fraction
- cell proliferation
- cell cycle arrest
- signaling pathway
- multidrug resistant
- oxidative stress
- pi k akt
- contrast enhanced
- ultrasound guided
- patient reported