MDSCs are induced after experimental blunt chest trauma and subsequently alter antigen-specific T cell responses

Yvonne Hüsecken,Monika Kustermann,Malena Klingspor,Sonja Braumüller,Sylvia Muche,Markus Huber-Lang,Annette Palmer,Klaus-Michael Debatin,Gudrun Strauss

doi:10.1038/s41598-017-13019-6

Yvonne Hüsecken, Monika Kustermann + Show 7 more

Open Access

https://doi.org/10.1038/s41598-017-13019-6

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Abstract

Severe blunt chest trauma (TxT) induces a strong inflammatory response with posttraumatic immune suppression pointing to an impaired adaptive immune response. Since CD11b+Gr-1+-expressing myeloid-derived suppressor cells (MDSCs) are induced after inflammation and suppress T cell responses, MDSC induction and their impact on T cell functions was analysed in an experimental TxT model. MDSCs were induced preferentially in the lung until 24 hours after TxT. Although MDSC numbers were only faintly increased in the spleen, splenic MDSCs isolated after TxT strongly inhibited alloantigen-induced T cell proliferation in vitro. Suppressive activity correlated with increased expression of arginase-1 and iNOS. MDSCs also prevented antigen-induced T cell expansion in vivo, since staphylococcus enterotoxin B (SEB)-induced proliferation of vβ8+ T cells was impaired in TxT mice in the presence of CD11b+Gr-1+ cells. Surprisingly, MDSCs were not involved in shifting T cells into Th2 cells, characterized by the secretion of cytokines impairing cell-mediated immunity and promoting immunosuppression. Instead, the presence of CD11b+Gr-1+ cells was required for efficient IL-2, IFN-γ and TNFα production after antigenic stimulation, indicating, that elevation of MDSCs early after traumatic injuries might contribute to restrict the initial inflammatory response by alleviating T cell expansion, however, without impeding Th1 functions.

Highlights

Blunt chest trauma (TxT) has a strong impact on the morbidity and mortality of patients regardless whether it is combined with other injuries or occurred in an isolated manner[1,2]
To clarify whether Myeloid-derived suppressor cells (MDSCs) are induced after blunt chest trauma, spleen and lungs of sham- and TxT-treated animals were analysed at different time points after trauma induction and absolute numbers of MDSCs were determined by staining cells for CD11b and Gr-1 (Fig. 1a)
The initial strong activation of the innate immune response is counterbalanced by a suppression of adaptive immunity favouring infectious complications, sepsis and late onset of multi organ dysfunction syndrome (MODS)

Summary

Introduction

Blunt chest trauma (TxT) has a strong impact on the morbidity and mortality of patients regardless whether it is combined with other injuries or occurred in an isolated manner[1,2]. TxT triggers a local immune response, followed by a systemic inflammation causing posttraumatic immunosuppression characterized by an impaired adaptive immune response and an increased infection risk[3,4,5]. The transient increase in inflammatory mediators impacts the ability of splenic lymphocytes and macrophages to produce cytokines indicating that lung contusion causes a systemic dysfunction of immunocompetent cells located distant from the site of injury[20]. Since cytokines such as IL-1β, IL-6 and G-CSF are released after TxT and are potent inducers of MDSCs, lung contusion might lead to MDSC accumulation and subsequent impairment of adaptive immunity. Irrespective of the model used, trauma-induced MDSCs inhibit the proliferative capacity of T cells[24,25,26]

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