Neutrophil differentiation into a unique hybrid population exhibiting dual phenotype and functionality of neutrophils and dendritic cells

Matsushima, Hironori; Geng, Shuo; Lu, Ran; Okamoto, Takashi; Yao, Yi; Mayuzumi, Nobuyasu; Kotol, Paul; Chojnacki, Benjamin J.; Miyazaki, Toru; Gallo, Richard L.; Takashima, Akira

doi:10.1182/blood-2012-07-445189

Cited by 172 publications

(222 citation statements)

References 50 publications

(58 reference statements)

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“…Neutrophils can acquire macrophage (34) or dendritic phenotypes (10), and such hybrid neutrophil populations with APC-like properties participate in adaptive immune responses (10). In the context of a tumor, the neutrophil subsets generated in the cytokine/chemokine environment can affect tumor growth by influencing CD8 T-cell activation (35).…”

Section: Discussionmentioning

confidence: 99%

“…Neutrophils can induce an adaptive immune response after migrating to the lymph nodes (8) and efficiently crossprime naïve T cells (9). In the presence of a granulocyte macrophage-colony-stimulating factor (GM-CSF) (10), tumor necrosis factor (TNF)-α, interleukin (IL)-4 (11), or interferon (IFN)-γ (12), neutrophils can adopt an antigen-presenting cell (APC) phenotype, thus triggering T-cell activation. In the context of VACV infection, neutrophils generate virus-specific memory CD8 T cells, transporting antigens from the dermis to the bone marrow (BM) (13).…”

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confidence: 99%

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NFκB activation by modified vaccinia virus as a novel strategy to enhance neutrophil migration and HIV-specific T-cell responses

Pilato¹,

Mejías-Pérez²,

Zonca

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Neutrophils are antigen-transporting cells that generate vaccinia virus (VACV)-specific T-cell responses, yet how VACV modulates neutrophil recruitment and its significance in the immune response are unknown. We generated an attenuated VACV strain that expresses HIV-1 clade C antigens but lacks three specific viral genes (A52R, K7R, and B15R). We found that these genes act together to inhibit the NFκB signaling pathway. Triple ablation in modified virus restored NFκB function in macrophages. After virus infection of mice, NFκB pathway activation led to expression of several cytokines/chemokines that increased the migration of neutrophil populations (Nα and Nβ) to the infection site. Nβ cells displayed features of antigen-presenting cells and activated virus-specific CD8 T cells. Enhanced neutrophil trafficking to the infection site correlated with an increased T-cell response to HIV vector-delivered antigens. These results identify a mechanism for poxvirus-induced immune response and alternatives for vaccine vector design.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

NFκB activation by modified vaccinia virus as a novel strategy to enhance neutrophil migration and HIV-specific T-cell responses

Pilato¹,

Mejías-Pérez²,

Zonca

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…In mice, neutrophils were recently shown to differentiate into ''neutrophil-DC hybrids'' that express markers typical of both neutrophils and DCs [81,82]. Of note, those intermediate cells exhibit a blend of neutrophil features such as phagocytosis, release of neutrophil extracellular traps and bacterial killing, and APC properties including DC-like morphology and migration, cytokine production and antigen presentation to naive CD4 + T cells.…”

Section: Interaction With Neutrophils: Unexpected Generation Of Apclimentioning

confidence: 99%

“…As a result of this crosstalk, neutrophils receive potent signals that trigger a substantial extension of their life span and allow them to acquire distinct phenotypes and functions including the capacity to facilitate monocyte differentiation and DC maturation, and to interact with T cells [78][79][80]. It is this intriguing APC-like aspect of neutrophil biology that is most relevant to this review.In mice, neutrophils were recently shown to differentiate into ''neutrophil-DC hybrids'' that express markers typical of both neutrophils and DCs [81,82]. Of note, those intermediate cells exhibit a blend of neutrophil features such as phagocytosis, release of neutrophil extracellular traps and bacterial killing, and APC properties including DC-like morphology and migration, cytokine production and antigen presentation to naive CD4 + T cells.…”

mentioning

confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

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a b s t r a c tUnconventional T cells are gaining center stage as important effector and regulatory cells that orchestrate innate and adaptive immune responses. Human Vc9/Vd2 T cells are amongst the best understood unconventional T cells, as they are easily accessible in peripheral blood, can readily be expanded and manipulated in vitro, respond to microbial infections in vivo and can be exploited for novel tumor immunotherapies. We here review findings that suggest that Vc9/Vd2 T cells, and possibly other unconventional human T cells, play an important role in bridging innate and adaptive immunity by promoting the activation and differentiation of various types of antigen-presenting cells (APCs) and even turning into APCs themselves, and thereby pave the way for antigen-specific effector responses and long-term immunological memory. Although the direct physiological relevance for most of these mechanisms still needs to be demonstrated in vivo, these findings may have implications for novel therapies, diagnostic tests and vaccines.Ó 2015 Published by Elsevier Inc. Introduction cd T cells represent a third lineage of lymphocytes expressingre-arranged antigen receptors that co-evolved with 'classical' B cells and ab T cells over 400 million years, arguing for a crucial and non-redundant contribution of each lymphocyte to effective immune responses, and hence the evolutionary survival of all jawed vertebrate species [1]. 30 years have passed since the accidental and unexpected cloning of the cd T cell receptor (TCR) and the subsequent realization that ab T cells and cd T cells are fundamentally different with respect to the types of antigens they recognize and the distinct effector functions triggered upon such recognition. However, the manifold contributions of cd T cells to homeostasis, inflammation, infection and tumor surveillance have historically been neglected and are only beginning to be integrated into comprehensive models of the immune system [1][2][3][4][5][6][7].1. Innate-like pattern recognition by human Vc9/Vd2 T cells Like other 'unconventional' T cells carrying an ab TCR such as mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells, cd T cells are characterized by a markedly restrictedTCR usage that allows them to recognize self and non-self molecules in the absence of classical antigen presentation via MHC I or MHC II. Vc9/Vd2 + cd T cells represent the major cd T cell subset in human peripheral blood where they typically comprise 1-5% in healthy adults [8]. In many microbial infections, Vc9/Vd2 T cells increase locally and/or systemically [9,10] and can reach in excess of 50% of all peripheral T cells within a matter of days [11], revealing a fundamental role of this unconventional T cell population in acute disease and suggesting their exploitation for diagnostic and therapeutic purposes [12][13][14]. Vc9/Vd2 T cells uniformly respond to a class of low molecular weight molecules often referred to as 'phosphoantigens' that represent metabolites of the isoprenoid biosynthesis...

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“…В связи с этим, все фагоцитирующие нейтрофилы были разделены на фракции: ак-тивно фагоцитирующие клетки и слабо фагоци-тирующие. Действительно, субпопуляционная гетерогенность нейтрофильных гранулоцитов отмечена в ряде исследований [8,13,15,17]. Дока-зано, что различные субпопуляции нейтрофилов по разному реализуют свою функциональную активность при воспалительных и онкологичес-ких заболеваниях.…”

Section: Discussionunclassified

Phagocytic Activity and Blood Neutrophils Respiratory Burst State Features Amongst Widespread Purulent Peritonitis Patients in the Postoperative Period Dynamics

Савченко

Гвоздев

Борисов

et al. 2017

Russian Journal of Infection and Immunity

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Резюме. Целью исследования явилось изучение фагоцитарной активности и состояния респираторного взрыва нейтрофилов крови у больных распространенным гнойным перитонитом (РГП) в динамике послеоперацион-ного периода. Обследованы пациенты с острыми хирургическими заболеваниями и травмами органов брюш-ной полости, осложнившимися РГП. Забор крови производили перед операцией (дооперационный период), а также на 7, 14 и 24 сутки послеоперационного периода. Уровень фагоцитоза нейтрофилов определяли мето-дом проточной цитометрии с помощью FITC-меченного стафилококкового белка А. Подсчитывали процент флуоресцирующих нейтрофилов (определяли как фагоцитарный индекс -ФИ) и средний уровень флуорес-ценции клеток (фагоцитарное число -ФЧ). По интенсивности флуоресценции разделяли нейтрофилы на ак-тивно фагоцитирующие (с высоким уровнем ФЧ) и слабо фагоцитирующие (с низким уровнем ФЧ). Состо-яние респираторного взрыва нейтрофильных гранулоцитов исследовали с помощью хемилюминесцентного анализа. Установлено, что у больных РГП уже в дооперационном периоде повышена фагоцитарная активность нейтрофильных гранулоцитов крови. Максимум фагоцитарной активности наблюдается на 7 сутки послеопе-рационного периода и к 24 суткам количество фагоцитирующих клеток снижается до контрольного уровня, тогда как фагоцитарная активность клеток остается на дооперационном уровне. В дооперационном периоде у больных РГП количество активно фагоцитирующих нейтрофилов крови в 3,3 раза превышает число слабо фагоцитирующих клеток. К концу периода наблюдения количество активно и слабо фагоцитирующих ней-трофилов нормализуется. При исследовании состояния респираторного взрыва в нейтрофилах больных РГП

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Neutrophil differentiation into a unique hybrid population exhibiting dual phenotype and functionality of neutrophils and dendritic cells

Abstract: Key Points Both immature and mature neutrophils differentiate into a previously unrecognized hybrid population when cultured with GM-CSF. The resulting hybrids exhibit dual phenotype and functionality of both neutrophils and dendritic cells.

Cited by 172 publications

References 50 publications

NFκB activation by modified vaccinia virus as a novel strategy to enhance neutrophil migration and HIV-specific T-cell responses

NFκB activation by modified vaccinia virus as a novel strategy to enhance neutrophil migration and HIV-specific T-cell responses

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Phagocytic Activity and Blood Neutrophils Respiratory Burst State Features Amongst Widespread Purulent Peritonitis Patients in the Postoperative Period Dynamics

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