Specific MAIT cell behaviour among innate-like T lymphocytes in critically ill patients with severe infections
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In between innate and adaptive immunity, the recently identified innate-like mucosal-associated invariant T (MAIT) lymphocytes display specific reactivity to non-streptococcal bacteria. Whether they are involved in bacterial sepsis has not been investigated. We aimed to assess the number and the time course of circulating innate-like T lymphocytes (MAIT, NKT and γδ T cells) in critically ill septic and non-septic patients and to establish correlations with the further development of intensive care unit (ICU)-acquired infections.
We prospectively enrolled consecutive patients with severe sepsis and septic shock. Controls were critically ill patients with non-septic shock and age-matched healthy subjects. Circulating innate-like lymphocytes were enumerated using a flow cytometry assay at day 1, 4 and 7.
One hundred and fifty six patients (113 severe bacterial infections, 36 non-infected patients and 7 patients with severe viral infections) and 26 healthy subjects were enrolled into the study. Patients with severe bacterial infections displayed an early decrease in MAIT cell count [median 1.3/mm3; interquartile range (0.4–3.2)] as compared to control healthy subjects [31.1/mm3 (12.1–45.2)], but also to non-infected critically ill patients [4.3/mm3 (1.4–13.2)] (P < 0.0001 for all comparisons). In contrast NKT and γδ T cell counts did not differ between patients groups. The multivariate analysis identified non-streptococcal bacterial infection as an independent determinant of decrease in MAIT cell count. Furthermore, the incidence of ICU-acquired infections was higher in patients with persistent MAIT cell depletion.
This large human study provides valuable information about MAIT cells in severe bacterial infections. The persistent depletion of MAIT cells is associated with the further development of ICU-acquired infections.
KeywordsInnate-like lymphocytes Septic shock Nosocomial infection Sepsis-induced immunosuppression
We are indebted to Professor A. Brezin (Department of Ophtalmology, Cochin Hospital) for including age-matched control subjects, and to Dr. N. Chapuis (Hematology laboratory, Cochin Hospital) and the Cochin Cytometry and Immunobiology Facility for technical help. This work was supported by grants from the European Society of Intensive Care Medicine (ECCRN Clinical Research Award 2010) and from the French Health Department (Inserm/DGOS 2011). D.G. was a recipient of a “Poste d’Accueil CNRS-CEA/APHP.” The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Conflicts of interest
J.P.M. has been a consultant to MSD, LFB, Astrazeneca, Astellas, Eli Lilly and Brahms and has received research funding from Eli Lilly. O.L. received royalties from Biolegend for the anti-Vα7.2 antibody. F.P. gave a lecture for LFB. J.D.C is the current president of European Society of Intensive Care Medicine. The other authors have no conflicts of interest.
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