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Specific MAIT cell behaviour among innate-like T lymphocytes in critically ill patients with severe infections

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgments

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.

Author information

Authors and Affiliations

  1. Réanimation médicale, Hôpital Cochin AP-HP, 27 rue du Faubourg Saint Jacques, 75014, Paris, France

    David Grimaldi, Bertrand Sauneuf, Jean-Daniel Chiche, Jean-Paul Mira & Frédéric Pène

  2. Institut Cochin INSERM U1016, Paris, France

    David Grimaldi, Christophe Rousseau, Fatah Ouaaz, Jean-Daniel Chiche, Jean-Paul Mira & Frédéric Pène

  3. CNRS UMR8104, Paris, France

    David Grimaldi, Christophe Rousseau, Fatah Ouaaz, Jean-Daniel Chiche, Jean-Paul Mira & Frédéric Pène

  4. Université Paris Descartes, Sorbonne Paris Cité, Paris, France

    David Grimaldi, Agnès Dechartres, Christophe Rousseau, Fatah Ouaaz, Jean-Daniel Chiche, Jean-Paul Mira & Frédéric Pène

  5. Réanimation médico-chirurgicale, Centre Hospitalier de Versailles, Le Chesnay, France

    David Grimaldi

  6. Institut Curie, Biologie des Tumeurs, Paris, France

    Lionel Le Bourhis, Maud Milder, Delphine Louis & Olivier Lantz

  7. INSERM U932, Paris, France

    Lionel Le Bourhis, Maud Milder, Delphine Louis & Olivier Lantz

  8. Centre d’investigation clinique CICBT507, Institut Curie/Institut Gustave Roussy, Paris, France

    Lionel Le Bourhis, Maud Milder, Delphine Louis & Olivier Lantz

  9. Centre d’épidémiologie clinique, Hôpital Hotel-Dieu, AP-HP, Paris, France

    Agnès Dechartres

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  1. David Grimaldi
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  2. Lionel Le Bourhis
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  3. Bertrand Sauneuf
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  7. Maud Milder
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  8. Delphine Louis
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  9. Jean-Daniel Chiche
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  11. Olivier Lantz
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  12. Frédéric Pène
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Corresponding authors

Correspondence to David Grimaldi or Frédéric Pène.

Additional information

A related article can be found at: doi: 10.1007/s00134-013-3141-3.

Take-home message: The innate-like lymphocytes called mucosal-associated invariant T (MAIT) cells are specifically decreased in patients with severe bacterial infections and their changes over time impact the further development of ICU-acquired infections. These results appear specific to MAIT cells among other innate-like T lymphocytes and add MAIT cell depletion to the spectrum of sepsis-induced immunosuppression.

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Grimaldi, D., Le Bourhis, L., Sauneuf, B. et al. Specific MAIT cell behaviour among innate-like T lymphocytes in critically ill patients with severe infections. Intensive Care Med 40, 192–201 (2014). https://doi.org/10.1007/s00134-013-3163-x

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  • DOI: https://doi.org/10.1007/s00134-013-3163-x

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