Tumor‐induced myeloid‐derived suppressor cell subsets exert either inhibitory or stimulatory effects on distinct CD8+ T‐cell activation events

Tumor growth coincides with an accumulation of myeloid‐derived suppressor cells (MDSCs), which exert immune suppression and which consist of two main subpopulations, known as monocytic (MO) CD11b⁺CD115⁺Ly6G^?Ly6C^high MDSCs and granulocytic CD11b⁺CD115^?Ly6G⁺Ly6C^int polymorphonuclear (PMN)‐MDSCs. However, whether these distinct MDSC subsets hamper all aspects of early CD8⁺ T‐cell activation — including cytokine production, surface marker expression, survival, and cytotoxicity — is currently unclear. Here, employing an in vitro coculture system, we demonstrate that splenic MDSC subsets suppress antigen‐driven CD8⁺ T‐cell proliferation, but differ in their dependency on IFN‐γ, STAT‐1, IRF‐1, and NO to do so. Moreover, MO‐MDSC and PMN‐MDSCs diminish IL‐2 levels, but only MO‐MDSCs affect IL‐2Rα (CD25) expression and STAT‐5 signaling. Unexpectedly, however, both MDSC populations stimulate IFN‐γ production by CD8⁺ T cells on a per cell basis, illustrating that some T‐cell activation characteristics are actually stimulated by MDSCs. Conversely, MO‐MDSCs counteract the activation‐induced change in CD44, CD62L, CD162, and granzyme B expression, while promoting CD69 and Fas upregulation. Together, these effects result in an altered CD8⁺ T‐cell adhesiveness to the extracellular matrix and selectins, sensitivity to FasL‐mediated apoptosis, and cytotoxicity. Hence, MDSCs intricately influence different CD8⁺ T‐cell activation events in vitro, whereby some parameters are suppressed while others are stimulated.     

IFN‐γ regulates survival and function of tumor‐induced CD11b+Gr‐1high myeloid derived suppressor cells by modulating the anti‐apoptotic molecule Bcl2a1

Myeloid derived suppressor cells (MDSCs) play a critical role in suppression of immune responses in cancer and inflammation. Here, we describe how regulation of Bcl2a1 by cytokines controls the suppressor function of CD11b⁺Gr‐1^high granulocytic MDSCs. Coculture of CD11b⁺Gr‐1^high granulocytic MDSCs with antigen‐stimulated T cells and simultaneous blockade of IFN‐γ by the use of anti‐IFN‐γ blocking antibody, IFN‐γ^?/? effector T cells, IFN‐γR^?/? MDSCs or STAT1^?/? MDSCs led to upregulation of Bcl2a1 in CD11b⁺Gr‐1^high cells, improved survival, and enhanced their suppressor function. Molecular studies revealed that GM‐CSF released by antigen‐stimulated CD8⁺ T cells induced Bcl2a1 upregulation, which was repressed in the presence of IFN‐γ by a direct interaction of phosphorylated STAT‐1 with the Bcl2a1 promotor. Bcl2a1 overexpressing granulocytic MDSCs demonstrated prolonged survival and enhanced suppressor function in vitro. Our data suggest that IFN‐γ/ STAT1‐dependent regulation of Bcl2a1 regulates survival and thereby suppressor function of granulocytic MDSCs.     

Impaired antigen‐specific lymphocyte priming in mice after Toll‐like receptor 4 activation via induction of monocytic myeloid‐derived suppressor cells

In sepsis, the pathology involves a shift from a proinflammatory state toward an immunosuppressive phase. We previously showed that an agonistic anti‐TLR4 antibody induced long‐term endotoxin tolerance and suppressed antigen‐specific secondary IgG production when primed prior to immunization with antigen. These findings led us to speculate that TLR4‐induced innate tolerance due to primary infection causes an immunosuppressive pathology in sepsis. Therefore, the mechanism underlying impaired antigen‐specific humoral immunity by the TLR4 antibody was investigated. We showed, in a mouse model, that primary antigen‐specific IgG responses were impaired in TLR4 antibody‐induced tolerized mice, which was the result of reduced numbers of antigen‐specific GC B cells and plasma cells. Ovalbumin‐specific CD4 and CD8 T‐cell responses were impaired in TLR4 antibody‐injected OT‐I and ‐II transgenic mice ex vivo. Adoptive transfer studies demonstrated suppression of OVA‐specific CD4 and CD8 T‐cell responses by the TLR4 antibody in vivo. The TLR4 antibody induced Gr1⁺CD11b⁺ myeloid‐derived suppressor cell (MDSC) expansion with suppression of T‐cell activation. Monocytic MDSCs were more suppressive and exhibited higher expression of PD‐L1 and inducible nitric oxidase compared with granulocytic MDSCs. In conclusion, immune tolerance conferred by TLR4 activation induces the expansion of monocytic MDSCs, which impairs antigen‐specific T‐cell priming and IgG production.     

Gr‐1 antibody induces STAT signaling,macrophage marker expression and abrogation of myeloid‐derived suppressor cell activity in BM cells

The Gr‐1 (RB6‐8C5) Ab binds with high affinity to mouse Ly‐6G molecules and to a lower extent to Ly‐6C and has been widely used for cell depletion in infected or tumor‐bearing mice. Here we found that Gr‐1 treatment of BM cells in vitro and in vivo showed no depleting effects. The epitope recognized by the Gr‐1 Ab overlapped with Ly‐6G (1A8 Ab) but not Ly‐6C (ER‐MP20 Ab). In vitro the Gr‐1 Ab transmitted signals via STAT‐1, STAT‐3 and STAT‐5 into BM cells, similar to GM‐CSF. In healthy mice injected with the Gr‐1 Ab, the Ab remained attached to the surface of myeloid cells for at least four days. Gr‐1 Ab induced myeloid cell expansion, upregulation of macrophage markers, but not the DC marker CD11c. Suppressor activity of two distinct Gr‐1^high and Gr‐1^low expressing BM‐myeloid‐derived suppressor cell subsets was transiently ablated by Gr‐1 Ab injection. Depleting effects of Gr‐1 Ab could only be observed on inflammatory Ly‐6C^intLy‐6G^high neutrophils from the peritoneal cavity, which occurred via apoptosis and was associated with the absence of Mcl‐1 expression. Together, Gr‐1 Ab induces signals leading to myelopoiesis and affects myeloid‐derived suppressor cell activity, suggesting functional roles for Ly‐6C/G molecules in macrophage differentiation and neutrophil apoptosis.     

Functional characterization of myeloid‐derived suppressor cell subpopulations during the development of experimental arthritis

Recent evidence indicates the existence of subpopulations of myeloid‐derived suppressor cells (MDSCs) with distinct phenotypes and functions. Here, we characterized the role of MDSC subpopulations in the pathogenesis of autoimmune arthritis in a collagen‐induced arthritis (CIA) mouse model. The splenic CD11b⁺Gr‐1⁺ MDSC population expanded in CIA mice, and these cells could be subdivided into polymorphonuclear (PMN) and mononuclear (MO) MDSC subpopulations based on Ly6C and Ly6G expression. During CIA, the proportion of splenic MO‐MDSCs was increased in association with the severity of joint inflammation, while PMN‐MDSCs were decreased. MO‐MDSCs expressed higher levels of surface CD40 and CD86 protein, but lower levels of Il10, Tgfb1, Ccr5, and Cxcr2 mRNA. PMN‐MDSCs exhibited a more potent capacity to suppress polyclonal T‐cell proliferation in vitro, compared with MO‐MDSCs. Moreover, the adoptive transfer of PMN‐MDSCs, but not MO‐MDSCs, decreased joint inflammation, accompanied by reduced levels of serum cytokine secretion and the frequencies of Th1 and Th17 cells in draining lymph nodes. These results suggest that there could be a shift from potently suppressive PMN‐MDSCs to poorly suppressive MO‐MDSCs during the development of experimental arthritis, which might reflect the failure of expanded MDSCs to suppress autoimmune arthritis.     

Polysaccharide Agaricus blazei Murill stimulates myeloid derived suppressor cell differentiation from M2 to M1 type,which mediates inhibition of tumour immune‐evasion via the Toll‐like receptor 2 pathway

Gr‐1⁺ CD11b⁺ myeloid‐derived suppressor cells (MDSCs) accumulate in tumor‐bearing animals and play a critical negative role during tumor immunotherapy. Strategies for inhibition of MDSCs are expected to improve cancer immunotherapy. Polysaccharide Agaricus blazei Murill (pAbM) has been found to have anti‐cancer activity, but the underlying mechanism of this is poorly understood. Here, pAbM directly activated the purified MDSCs through inducing the expression of interleukin‐6 (IL‐6), IL‐12, tumour necrosis factor and inducible nitric oxide synthase (iNOS), CD86, MHC II, and pSTAT1 of it, and only affected natural killer and T cells in the presence of Gr‐1⁺ CD11b⁺ monocytic MDSCs. On further analysis, we demonstrated that pAbM could selectively block the Toll‐like receptor 2 (TLR2) signal of Gr‐1⁺ CD11b⁺ MDSCs and increased their M1‐type macrophage characteristics, such as producing IL‐12, lowering expression of Arginase 1 and increasing expression of iNOS. Extensive study showed that Gr‐1⁺ CD11b⁺ MDSCs by pAbM treatment had less ability to convert the CD4⁺ CD25^? cells into CD4⁺ CD25⁺ phenotype. Moreover, result from selective depletion of specific cell populations in xenograft mice model suggested that the anti‐tumour effect of pAbM was dependent on Gr‐1⁺ CD11b⁺ monocytes, nether CD8⁺ T cells nor CD4⁺ T cells. In addition to, pAbM did not inhibit tumour growth in TLR2^–/– mice. All together, these results suggested that pAbM, a natural product commonly used for cancer treatment, was a specific TLR2 agonist and had potent anti‐tumour effects through the opposite of the suppressive function of Gr‐1⁺ CD11b⁺ MDSCs.     

Expansion of CD11b<Superscript>+</Superscript>Ly6G<Superscript>high</Superscript> and CD11b<Superscript>+</Superscript>CD49d<Superscript>+</Superscript> myeloid cells with suppressive potential in mice with chronic inflammation and light-at-night-induced circadian disruption

Objective

Myeloid-derived suppressor cells (MDSCs) are important negative regulators of immune processes in cancer and other pathological conditions. We suggested that MDSCs play a key role in pathogenesis of chronic inflammation, which precedes and, to a certain extent, induces carcinogenesis. The present study aimed at investigation of MDSCs arising during chronic inflammation and light-at-night (LN)-induced stress, which is shown to accelerate chronic diseases.

Subjects

67 CD-1 mice and in vitro MDSC cultures.

Treatment

Adjuvant arthritis was induced by a subdermal injection of complete Freund’s adjuvant. LN was induced by illumination of 750 lx at night.

Methods

Flow cytometry for evaluation of cell phenotypes and MTT standard test for cell proliferation were used.

Results

Increased levels of splenic CD11b⁺Ly6G^high and CD11b⁺CD49d⁺ myeloid cells possessing suppressive potential in mice with adjuvant arthritis are shown. LN amplifies the process of CD11b⁺Ly6G^high expansion in mice with adjuvant arthritis. Expression of CD62L and CD195 is elevated on the myeloid cells during exposure to LN.

Conclusions

Our study raises the possibility that CD11b⁺Ly6G^high and CD11b⁺CD49d⁺ MDSCs play an important role in the induction of immunosuppressive environment typical for chronic inflammation. Also, LN can affect immune responses during chronic inflammation through recruitment of MDSCs from the bone marrow.

     

Galectin‐9 expands immunosuppressive macrophages to ameliorate T‐cell‐mediated lung inflammation

Galectin‐9 (Gal‐9) plays pivotal roles in the modulation of innate and adaptive immunity to suppress T‐cell‐mediated autoimmune models. However, it remains unclear if Gal‐9 plays a suppressive role for T‐cell function in non‐autoimmune disease models. We assessed the effects of Gal‐9 on experimental hypersensitivity pneumonitis induced by Trichosporon asahii. When Gal‐9 was given subcutaneously to C57BL/6 mice at the time of challenge with T. asahii, it significantly suppressed T. asahii‐induced lung inflammation, as the levels of IL‐1, IL‐6, IFN‐γ, and IL‐17 were significantly reduced in the BALF of Gal‐9‐treated mice. Moreover, co‐culture of anti‐CD3‐stimulated CD4 T cells with BALF cells harvested from Gal‐9‐treated mice on day 1 resulted in diminished CD4 T‐cell proliferation and decreased levels of IFN‐γ and IL‐17. CD11b⁺Ly‐6C^highF4/80⁺ BALF M? expanded by Gal‐9 were responsible for the suppression. We further found in vitro that Gal‐9, only in the presence of T. asahii, expands CD11b⁺Ly‐6C^highF4/80⁺ cells from BM cells, and the cells suppress T‐cell proliferation and IFN‐γ and IL‐17 production. The present results indicate that Gal‐9 expands immunosuppressive CD11b⁺Ly‐6C^high M? to ameliorate Th1/Th17 cell‐mediated hypersensitivity pneumonitis.     

β‐Glucan enhances antitumor immune responses by regulating differentiation and function of monocytic myeloid‐derived suppressor cells

Myeloid‐derived suppressor cells (MDSCs) accumulate in tumor‐bearing hosts and play a major role in tumor‐induced immunosuppression, which hampers effective immuno‐therapeutic approaches. β‐Glucans have been reported to function as potent immuno‐modulators to stimulate innate and adaptive immune responses, which contributes to their antitumor property. Here, we investigated the effect of particulate β‐glucans on MDSCs and found that β‐glucan treatment could promote the differentiation of M‐MDSCs (monocytic MDSCs) into a more mature CD11c⁺ F4/80⁺ Ly6C^low population via dectin‐1 pathway in vitro, which is NF‐κB dependent, and the suppressive function of M‐MDSCs was significantly decreased. Treatment of orally administered yeast‐derived particulate β‐glucan drastically downregulated MDSCs but increased the infiltrated DCs and macrophages in tumor‐bearing mice, thus eliciting CTL and Th1 responses, inhibiting the suppressive activity of regulatory T cells, thereby leading to the delayed tumor progression. We show here for the first time that β‐glucans induce the differentiation of MDSCs and inhibit the regulatory function of MDSCs, therefore revealing a novel mechanism for β‐glucans in immunotherapy and suggesting their potential clinical benefit.     

Mature resting Ly6Chigh natural killer cells can be reactivated by IL‐15

Mature NK cells are heterogeneous as to their expression levels of cell surface molecules. However, the functional differences and physiological roles of each NK‐cell subset are not fully understood. In this study, we report that based on the Ly6C expression levels, mature C57BL/6 murine NK cells can be subdivided into Ly6C^low and Ly6C^high subsets. Ly6C^high NK cells are in an inert state as evidenced by the production of lower levels of IFN‐γ and granzyme B, and they exhibit poorer proliferative potential than Ly6C^low NK cells. In addition, adoptive transfer experiments revealed that Ly6C^high NK cells are derived from Ly6C^low NK cells in the steady state. These results strongly suggest that Ly6C^high NK cells are resting cells in the steady state. However, in vitro, Ly6C^high NK cells become Ly6C^low NK cells with strong effector functions upon stimulation with IL‐15. Moreover, Ly6C^high NK cells also revert to Ly6C^low NK cells in vivo upon injection of the IL‐15 inducers polyI:C and CpG. Taken together, these results demonstrate the plasticity of mature NK cells and suggest that Ly6C^high NK cells are a reservoir of potential NK cells that allow effective and strong response to infections.     

Tumor‐induced CD11b+ Gr‐1+ myeloid‐derived suppressor cells exacerbate immune‐mediated hepatitis in mice in a CD40‐dependent manner

Immunosuppressive CD11b⁺Gr‐1⁺ myeloid‐derived suppressor cells (MDSCs) accumulate in the livers of tumor‐bearing (TB) mice. We studied hepatic MDSCs in two murine models of immune‐mediated hepatitis. Unexpectedly, treatment of TB mice with Concanavalin A (Con A) or α‐galactosylceramide resulted in increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum levels in comparison to tumor‐free mice. Adoptive transfer of hepatic MDSCs into naïve mice exacerbated Con A induced liver damage. Hepatic CD11b⁺Gr‐1⁺ cells revealed a polarized proinflammatory gene signature after Con A treatment. An IFN‐γ‐dependent upregulation of CD40 on hepatic CD11b⁺Gr‐1⁺ cells along with an upregulation of CD80, CD86, and CD1d after Con A treatment was observed. Con A treatment resulted in a loss of suppressor function by tumor‐induced CD11b⁺Gr‐1⁺ MDSCs as well as enhanced reactive oxygen species (ROS)‐mediated hepatotoxicity. CD40 knockdown in hepatic MDSCs led to increased arginase activity upon Con A treatment and lower ALT/AST serum levels. Finally, blockade of arginase activity in Cd40^?/? tumor‐induced myeloid cells resulted in exacerbation of hepatitis and increased ROS production in vivo. Our findings indicate that in a setting of acute hepatitis, tumor‐induced hepatic MDSCs act as proinflammatory immune effector cells capable of killing hepatocytes in a CD40‐dependent manner.     

Hierarchy of immunosuppressive strength among myeloid‐derived suppressor cell subsets is determined by GM‐CSF

CD11b⁺/Gr‐1⁺ myeloid‐derived suppressor cells (MDSC) contribute to tumor immune evasion by restraining the activity of CD8⁺ T‐cells. Two major MDSC subsets were recently shown to play an equal role in MDSC‐induced immune dysfunctions: monocytic‐ and granulocytic‐like. We isolated three fractions of MDSC, i.e. CD11b⁺/Gr‐1^high, CD11b⁺/Gr‐1^int, and CD11b⁺/Gr‐1^low populations that were characterized morphologically, phenotypically and functionally in different tumor models. In vitro assays showed that CD11b⁺/Gr‐1^int cell subset, mainly comprising monocytes and myeloid precursors, was always capable to suppress CD8⁺ T‐cell activation, while CD11b⁺/Gr‐1^high cells, mostly granulocytes, exerted appreciable suppression only in some tumor models and when present in high numbers. The CD11b⁺/Gr‐1^int but not CD11b⁺/Gr‐1^high cells were also immunosuppressive in vivo following adoptive transfer. CD11b⁺/Gr‐1^low cells retained the immunosuppressive potential in most tumor models. Gene silencing experiments indicated that GM‐CSF was necessary to induce preferential expansion of both CD11b⁺/Gr‐1^int and CD11b⁺/Gr‐1^low subsets in the spleen of tumor‐bearing mice and mediate tumor‐induced tolerance whereas G‐CSF, which preferentially expanded CD11b⁺/Gr‐1^high cells, did not create such immunosuppressive environment. GM‐CSF also acted on granulocyte–macrophage progenitors in the bone marrow inducing local expansion of CD11b⁺/Gr‐1^low cells. These data unveil a hierarchy of immunoregulatory activity among MDSC subsets that is controlled by tumor‐released GM‐CSF.     

Anti‐psoriatic effect of myeloid‐derived suppressor cells on imiquimod‐induced skin inflammation in mice

Myeloid‐derived suppressor cells (MDSCs) play an important role in controlling the immune response against cancer and in suppression of autoimmunity and allergic inflammation. However, the beneficial effects of MDSCs on the experimental mouse model of psoriasis have not been reported. Therefore, we investigated the anti‐psoriatic effect of MDSCs on IMQ‐induced skin inflammation in mice and explored the mechanisms involved. Our results showed that administration of MDSCs (1 × 10⁶ or 2 × 10⁶ cells) suppressed the development of IMQ‐induced skin inflammation in mice as exemplified by a significant reduction in clinical severity scores and was associated with a reduction of histopathological changes, including inflammatory infiltration, epidermal hyperplasia and hyperkeratosis. The immunosuppressive effect of MDSCs (1 × 10⁶ or 2 × 10⁶ cells) corresponded to the production of Th1 cytokines (TNF‐α, IFN‐γ) and Th17 cytokines (IL‐17A and IL‐23) in the serum and dorsal skin. Administration of MDSCs (1 × 10⁶ or 2 × 10⁶ cells) also inhibited splenomegaly. Moreover, an increased percentage of CD4⁺CD25⁺FoxP3⁺ regulatory T (Treg) cells and decreased percentage of Th1 and Th17 cells were found in mice treated with MDSCs. Taken together, these results imply that MDSCs have immunomodulatory and immunosuppressive effects on disease progression in a murine model of psoriasis and that MDSCs could be used in preventive or therapeutic strategies for the management of autoimmune inflammatory skin disorders, such as psoriasis.     

Myeloid‐derived suppressor cell activation by combined LPS and IFN‐γ treatment impairs DC development

Myeloid‐derived suppressor cells (MDSC) and DC are major controllers of immune responses against tumors or infections. However, it remains unclear how DC development and MDSC suppressor activity both generated from myeloid precursor cells are regulated. Here, we show that the combined treatment of BM‐derived MDSC with LPS plus IFN‐γ inhibited the DC development but enhanced MDSC functions, such as NO release and T‐cell suppression. This was not observed by the single treatments in vitro. In the spleens of healthy mice, we identified two Gr‐1^lowCD11b^highLy‐6C^highSSC^lowMo‐MDSC and Gr‐1^highCD11b^lowPMN‐MDSC populations with suppressive potential, whereas Gr‐1^highCD11b^high neutrophils and Gr‐1^lowCD11b^highSSC^low eosinophils were not suppressive. Injections of LPS plus IFN‐γ expanded these populations within the spleen but not LN leading to the block of the proliferation of CD8⁺ T cells. At the same time, their capacity to develop into DC was impaired. Together, our data suggest that spleens of healthy mice contain two subsets of MDSC with suppressive potential. A two‐signal‐program through combined LPS and IFN‐γ treatment expands and fully activates MDSC in vitro and in vivo.     

Co‐expression of TLR‐9 and MMP‐13 is associated with the degree of tumour differentiation in prostate cancer

In vitro experiments demonstrated that stimulation of Toll‐like receptor 9 (TLR‐9) by synthetic TLR‐9 ligands induces the invasion of TLR‐9‐expressing prostate cancer cells through matrix metalloproteinase 13 (MMP‐13). However, the clinical value of TLR‐9 and MMP‐13 co‐expression in the pathophysiology of the prostate is unknown. In the study, we evaluated the expression levels and clinical significance of the TLR‐9 and MMP‐13 in a series of prostate tissues. One hundred and eighty prostate tissues including prostate cancer (PCa) (n = 137), high‐grade prostatic intraepithelial neoplasia (HPIN) (n = 18) and benign prostatic hyperplasia (BPH) (n = 25) were immunostained for the TLR‐9 and MMP‐13 markers. Subsequently, the correlation between the TLR‐9 and MMP‐13 staining scores and clinicopathological parameters was obtained. Higher expressions of TLR‐9 and MMP‐13 were found in PCa and high‐grade prostatic intraepithelial neoplasia compared to benign prostatic hyperplasia tissues. Among PCa samples, a positive relationship was revealed between the MMP‐13 expression and Gleason score (P < 0.001). There was a significant correlation between TLR‐9 expression and regional lymph node involvement (P = 0.04). The expression patterns of TLR‐9 and MMP‐13 markers demonstrated a reciprocal significant correlation between the two markers in the same series of prostate samples (P < 0.001). Furthermore, the Gleason score of TLR‐9^high/MMP‐13^high and TLR‐9^low/MMP‐13^low phenotypes showed a significant difference (P = 0.002). Higher expressions of TLR‐9 and MMP‐13 can confer aggressive behaviour to PCa. Therefore, these markers may be used as a valuable target for tailored therapy of PCa.     

Neonatal myeloid derived suppressor cells show reduced apoptosis and immunosuppressive activity upon infection with Escherichia coli

Susceptibility to infection during the neonatal period and reduced control of inflammation in neonates are attributed to immunosuppression persisting from fetal life. Myeloid‐derived suppressor cells (MDSCs) are immature myeloid progenitors with suppressive activity and increased numbers in cord blood. We hypothesized that MDSCs contribute to innate host defence in neonates, paralleled by anti‐inflammatory signalling.Phagocytic activity, infection induced apoptosis, expression of B‐cell lymphoma (Bcl)‐2 family proteins, production of reactive oxygen species (ROS), cytokine production and T‐cell suppression of neonatal granulocytic‐MDSCs (G‐MDSCs) after infection with Escherichia coli (E. coli) were compared to neonatal autologous mature polymorphonuclear leukocytes (PMNs). Phagocytic activity of G‐MDSCs upon infection with E. coli was equal to that of mature PMNs, however, apoptosis of G‐MDSCs was decreased. G‐MDSCs showed enhanced Bcl‐2‐expression and lower ROS production compared to PMNs. Inhibition of Bcl‐2 reduced apoptosis rates of G‐MDSCs to that of mature PMNs. Induction of anti‐inflammatory transforming growth factor beta (TGF‐β) was enhanced, while pro‐inflammatory IL‐8 decreased in G‐MDSCs compared to PMNs. Infected G‐MDSCs strongly suppressed proliferation of T cells. We show a direct role of G‐MDSCs for anti‐bacterial host defence. Prolonged survival and anti‐inflammatory capacity suggest that G‐MDSCs are important for immune‐regulation after bacterial infection.