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    ABSTRACT: Polymorphonuclear neutrophils, besides their involvement in primary defense against infections - mainly through phagocytosis, generation of toxic molecules, release of enzymes, and formation of extracellular traps - are also becoming increasingly important for their contribution to the fine regulation in development of inflammatory and immune responses. These latter functions of neutrophils occur, in part, via their de novo production and release of a large variety of cytokines, including chemotactic cytokines (chemokines). Accordingly, the improvement in technologies for molecular and functional cell analysis, along with concomitant advances in cell purification techniques, have allowed the identification of a continuously growing list of neutrophil-derived cytokines, as well as the characterization of their biological implications in vitro and/or in vivo. This short review summarizes crucial concepts regarding the modalities of expression, release, and regulation of neutrophil-derived cytokines. It also highlights examples illustrating the potential implications of neutrophil-derived cytokines according to recent observations made in humans and/or in experimental animal models.
    Frontiers in Immunology 10/2014; 5:508. DOI:10.3389/fimmu.2014.00508
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    ABSTRACT: The early immune response to microbes is dominated by the recruitment of neutrophils whose primary function is to clear invading pathogens. However, there is emerging evidence that neutrophils play additional effector and regulatory roles. The present study demonstrates that human neutrophils assume Ag cross-presenting functions and suggests a plausible scenario for the local generation of APC-like neutrophils through the mobilization of unconventional T cells in response to microbial metabolites. Vγ9/Vδ2 T cells and mucosal-associated invariant T cells are abundant in blood, inflamed tissues, and mucosal barriers. In this study, both human cell types responded rapidly to neutrophils after phagocytosis of Gram-positive and Gram-negative bacteria producing the corresponding ligands, and in turn mediated the differentiation of neutrophils into APCs for both CD4(+) and CD8(+) T cells through secretion of GM-CSF, IFN-γ, and TNF-α. In patients with acute sepsis, circulating neutrophils displayed a similar APC-like phenotype and readily processed soluble proteins for cross-presentation of antigenic peptides to CD8(+) T cells, at a time when peripheral Vγ9/Vδ2 T cells were highly activated. Our findings indicate that unconventional T cells represent key controllers of neutrophil-driven innate and adaptive responses to a broad range of pathogens.
    The Journal of Immunology 08/2014; 193(7). DOI:10.4049/jimmunol.1401018 · 5.36 Impact Factor
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    ABSTRACT: Background/Aims: Neutrophils obtain immunosuppressive function during tumor development, yet the mechanisms are largely unknown. This study explored whether and how mesenchymal stromal cells (MSCs), the key component of tumor microenvironment, regulate the suppressive function of neutrophils. Methods: Immunosuppressive function of neutrophils was evaluated by T cell proliferation assay and 4T1 breast tumor model; molecular mechanisms were explored by transcriptional profiling, Real-time RT-PCR, arginase activity assay, and iNOS inhibition experiments. Results: After being cocultured with MSCs primed by TNF-α (TNF-MSCs), CD11b(+)Ly6G(+) neutrophils isolated from bone marrow of normal mice or spleen of tumor-bearing mice obtained immunosuppressive function to inhibit T cell proliferation in vitro, and to enhance 4T1 tumor progression in vivo. Moreover, arginase activity and expression of iNOS, saa3, some cytokines and chemokines and their receptors, were upregulated in neutrophils after co-culture with TNF-MSCs. Inhibition of iNOS activity attenuated the suppressive effect of TNF-MSC pre-cocultured neutrophils on T cell proliferation. Conclusion: MSCs program neutrophils into an immunosuppressive and tumor-promoting phenotype. © 2014 S. Karger AG, Basel.
    Cellular Physiology and Biochemistry 05/2014; 33(6):1802-1814. DOI:10.1159/000362959 · 3.55 Impact Factor