Emergence, origin, and function of neutrophil–dendritic cell hybrids in experimentally induced inflammatory lesions in mice

Geng, Shuo; Matsushima, Hironori; Okamoto, Takashi; Yao, Yi; Lu, Ran; Page, Kristen; Blumenthal, Robert; Ward, Nicole L.; Miyazaki, Toru; Takashima, Akira

doi:10.1182/blood-2012-07-445197

Cited by 85 publications

(105 citation statements)

References 48 publications

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“…98% of the IFN-g-expressing cells in lung digests are neutrophils, as marked by high expression levels of Ly6G. Recent reports have indicated that CD11c-expressing neutrophils arise during inflammation and may be important in bacterial clearance and antigen presentation by functioning as neutrophil-dendritic cell hybrids (39,40). The number of lung cells coexpressing CD11c and Ly6G was greater in WT mice with S. pneumoniae pneumonia compared with those given PBS (4.0 6 0.73 3 10 4 versus 0.13 6 0.04 3 10 4 [n = 4]; P , 0.05 using t test).…”

Section: Resultsmentioning

confidence: 99%

Mechanisms of Interferon-γ Production by Neutrophils and Its Function duringStreptococcus pneumoniaePneumonia

Gomez

Yamada

Martin

et al. 2015

Am J Respir Cell Mol Biol

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Bacterial pneumonia is a common public health problem associated with significant mortality, morbidity, and cost. Neutrophils are usually the earliest leukocytes to respond to bacteria in the lungs. Neutrophils rapidly sequester in the pulmonary microvasculature and migrate into the lung parenchyma and alveolar spaces, where they perform numerous effector functions for host defense. Previous studies showed that migrated neutrophils produce IFN-g early during pneumonia induced by Streptococcus pneumoniae and that early production of IFN-g regulates bacterial clearance. IFN-g production by neutrophils requires Rac2, Hck/Lyn/Fgr Src family tyrosine kinases, and NADPH oxidase. Our current studies examined the mechanisms that regulate IFN-g production by lung neutrophils during acute S. pneumoniae pneumonia in mice and its function. We demonstrate that IFN-g production by neutrophils is a tightly regulated process that does not require IL-12. The adaptor molecule MyD88 is critical for IFN-g production by neutrophils. The guanine nucleotide exchange factor CalDAG-GEFI modulates IFN-g production. The CD11/CD18 complex, CD44, Toll-like receptors 2 and 4, TRIF, and Nrf2 are not required for IFN-g production by neutrophils. The recently described neutrophil-dendritic cell hybrid cell, identified by its expression of Ly6G and CD11c, is present at low numbers in pneumonic lungs and is not a source of IFN-g. IFN-g produced by neutrophils early during acute S. pneumoniae pneumonia induces transcription of target genes in the lungs, which are critical for host defense. These studies underline the complexity of the neutrophil responses during pneumonia in the acute inflammatory response and in subsequent resolution or initiation of immune responses.

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Section: Resultsmentioning

confidence: 99%

Mechanisms of Interferon-γ Production by Neutrophils and Its Function duringStreptococcus pneumoniaePneumonia

Gomez

Yamada

Martin

et al. 2015

Am J Respir Cell Mol Biol

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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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“…96 On the other hand, has been described that neutrophils can have a APC-like phenotype expressing costimulatory molecules and activating CD4 C T cells polarizing to a TH1/ TH17 phenotype in inflammatory mouse model, but for hRSV infections this phenomenon has not been demonstrated yet. 97,98 This could be an important unexplored area because has been described that hRSV can infect human neutrophils. Indeed, it has been possible to measure F, G and N proteins and viral RNA on those cells, 99 suggesting that neutrophils can uptake virus in the airways of infected children and then present antigens to T cells, but further evidence is necessary to support this idea.…”

Section: An Adequate Cd4mentioning

confidence: 99%

Aberrant T cell immunity triggered by human Respiratory Syncytial Virus and human Metapneumovirus infection

et al. 2016

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Human Respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are the two major etiological viral agents of lower respiratory tract diseases, affecting mainly infants, young children and the elderly. Although the infection of both viruses trigger an antiviral immune response that mediate viral clearance and disease resolution in immunocompetent individuals, the promotion of long-term immunity appears to be deficient and reinfection are common throughout life. A possible explanation for this phenomenon is that hRSV and hMPV, can induce aberrant T cell responses, which leads to exacerbated lung inflammation and poor T and B cell memory immunity. The modulation of immune response exerted by both viruses include different strategies such as, impairment of immunological synapse mediated by viral proteins or soluble factors, and the induction of pro-inflammatory cytokines by epithelial cells, among others. All these viral strategies contribute to the alteration of the adaptive immunity in order to increase the susceptibility to reinfections.In this review, we discuss current research related to the mechanisms underlying the impairment of T and B cell immune responses induced by hRSV and hMPV infection. In addition, we described the role each virulence factor involved in immune modulation caused by these viruses.

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Emergence, origin, and function of neutrophil–dendritic cell hybrids in experimentally induced inflammatory lesions in mice

Abstract: Key Points Neutrophils differentiate into neutrophil–dendritic cell hybrids upon recruitment to sites of inflammation or infection. Hybrids play dual protective roles against bacterial infection by rapidly clearing bacteria and presenting bacterial antigens to T cells.

Cited by 85 publications

References 48 publications

Mechanisms of Interferon-γ Production by Neutrophils and Its Function duringStreptococcus pneumoniaePneumonia

Mechanisms of Interferon-γ Production by Neutrophils and Its Function duringStreptococcus pneumoniaePneumonia

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

Aberrant T cell immunity triggered by human Respiratory Syncytial Virus and human Metapneumovirus infection

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