Coactivation of Syk Kinase and MyD88 Adaptor Protein Pathways by Bacteria Promotes Regulatory Properties of Neutrophils

Zhang, Xiaoming; Majlessi, Laleh; Dériaud, Edith; Leclerc, Claude; Lo‐Man, Richard

doi:10.1016/j.immuni.2009.09.016

Cited by 276 publications

(305 citation statements)

References 47 publications

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“…12), were found to express IL-6 mRNA and to produce IL-6 when cultured for 14 h in vitro with 25 mM R848 or 10 mg ml À 1 LPS. By contrast, no IL-6 was measured in supernatants from bone marrow-derived neutrophils cultured under the same conditions, confirming previous findings 42 . In line with these results, only inflammatory peritoneal, but not bone marrow, neutrophils were found to express TLR7 and TLR8 mRNA (Fig.…”

Section: Il-6 Production By Murine Neutrophils In Vitro and In Vivosupporting

confidence: 90%

Chromatin remodelling and autocrine TNFα are required for optimal interleukin-6 expression in activated human neutrophils

et al. 2015

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Controversy currently exists about the ability of human neutrophils to produce IL-6. Here, we show that the chromatin organization of the IL-6 genomic locus in human neutrophils is constitutively kept in an inactive configuration. However, we also show that upon exposure to stimuli that trigger chromatin remodelling at the IL-6 locus, such as ligands for TLR8 or, less efficiently, TLR4, highly purified neutrophils express and secrete IL-6. In TLR8-activated neutrophils, but not monocytes, IL-6 expression is preceded by the induction of a latent enhancer located 14 kb upstream of the IL-6 transcriptional start site. In addition, IL-6 induction is potentiated by endogenous TNFa, which prolongs the synthesis of the IkBz co-activator and sustains C/EBPb recruitment and histone acetylation at IL-6 regulatory regions. Altogether, these data clarify controversial literature on the ability of human neutrophils to generate IL-6 and uncover chromatin-dependent layers of regulation of IL-6 in these cells.

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Section: Il-6 Production By Murine Neutrophils In Vitro and In Vivosupporting

confidence: 90%

Chromatin remodelling and autocrine TNFα are required for optimal interleukin-6 expression in activated human neutrophils

et al. 2015

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“…These findings suggest that NKT cells regulate IL-1β production during CLP-induced sepsis in an IFN-γ-independent manner. Several studies prior to ours demonstrated that neutrophils produce IL-10 in response to bacterial infection in a DAP12 adaptor-Syk kinase and MyD88-dependent manner [36], and constitute a major cell subset for producing IL-10 during sepsis [37,38]. Consistent with these findings, our experiments demonstrated that neutrophil deletion in WT mice decreases IL-10 and C5a levels in serum and peritoneal fluid compared with CD1d −/− mice during CLP-induced sepsis.…”

supporting

confidence: 90%

IFN‐γ‐producing NKT cells exacerbate sepsis by enhancing C5a generation via IL‐10‐mediated inhibition of CD55 expression on neutrophils

Kim

Ahn

et al. 2014

Eur J Immunol

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A role for NKT cells has been implicated in sepsis, but the mechanism by which NKT cells contribute to sepsis remains unclear. Here, we examined WT and NKT-cell-deficient mice of C57BL/6 background during cecal ligation and puncture-induced sepsis. The levels of C5a, IFN-γ, and IL-10 were higher in the serum and peritoneal fluid of WT mice than in those of CD1d −/− mice, while the mortality rate was lower in CD1d −/− mice than in WT mice. C5a blockade decreased mortality of WT mice during sepsis, whereas it did not alter that of CD1d −/− mice. As assessed by intracellular staining, NKT cells expressed IFN-γ, while neutrophils expressed IL-10. Upon coculture, IL-10-deficient NKT cells enhanced IL-10 production by WT, but not IFN-γR-deficient, neutrophils. Meanwhile, CD1d −/− mice exhibited high CD55 expression on neutrophils during sepsis, whereas those cells from WT mice expressed minimal levels of CD55. Recombinant IL-10 administration into CD1d −/− mice reduced CD55 expression on neutrophils. Furthermore, adoptive transfer of sorted WT, but not IFN-γ-deficient, NKT cells into CD1d −/− mice suppressed CD55 expression on neutrophils, but increased IL-10 and C5a levels. Taken together, IFN-γ-producing NKT cells enhance C5a generation via IL-10-mediated inhibition of CD55 expression on neutrophils, thereby exacerbating sepsis.Keywords: C5a r IFN-γ r Neutrophils r NKT cell r Sepsis Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionNKT cells are a distinct T-cell subset characterized by the expression of natural killer receptors and semi-invariant TCRs. These cells recognize glycolipids presented by CD1d, an MHC class I-like Correspondence: Dr. Doo Hyun Chung e-mail: doohyun@snu.ac.kr protein expressed by APCs [1]. During bacterial infection, TCRs on NKT cells directly recognize glycolipids derived from certain Gramnegative bacterial membranes [2,3] and can be activated by innate cytokines secreted by dendritic cells that have been activated by microorganisms [2,4]. Furthermore, LPS-mediated engagement of TLR4 directly activates NKT cells in terms of differential * These authors contributed equally to this work. Eur. J. Immunol. 2014Immunol. . 44: 2025Immunol. -2035 cytokine production, thereby regulating immune diseases [5]. These findings suggest that NKT cells, activated during immune responses against bacteria, regulate bacteria-mediated pathologic processes such as sepsis. Sepsis is a complex inflammatory dysregulation that causes multiple organ dysfunction and coagulopathy, often resulting in death [6,7]. Several studies have demonstrated that NKT cells promote LPS-or cecal ligation and puncture (CLP)-induced sepsis in mice through the production of . Consistent with these findings, two independent studies have demonstrated that treatment of C57BL/6 mice with anti-CD1d antibody enhances survival rates during CLP-induced sepsis [11,12], suggesting that NKT-cell-mediated promotion of sepsis depends on an interaction between CD1d and TCR...

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“…Murine neutrophils, which flood into the peritoneal cavity in large numbers, are a rich source of 20) although other cell types may well also contribute to the production of this cytokine (23,24). In this early period, when the IL-10 concentration in the peritoneum is high, the macrophages formed are of the MHC II lo type, whereas later, when the IL-10 concentration has fallen, the macrophages formed are of the MHC II hi type.…”

Section: Discussionmentioning

confidence: 99%

IL-10 Acts As a Developmental Switch Guiding Monocyte Differentiation to Macrophages during a Murine Peritoneal Infection

Nguyen

Tran

Müller

et al. 2012

The Journal of Immunology

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The peritoneal wash of BALB/c or C57BL/6 mice contains two populations of macrophages that differ in their level of expression of MHC class II (MHC II). Although both populations efficiently phagocytose bacteria in vivo, only the MHC IIlo population is effective at phagocytosing apoptotic cells in vivo and only the MHC IIhi population is effective at presenting Ag to T cells in vitro. Soon after induction of a peritoneal infection both of these macrophage populations are lost from the peritoneal wash fraction. Blood monocytes then enter the inflamed peritoneum and develop into new peritoneal macrophages. Whether these monocytes develop into MHC IIlo or into MHC IIhi macrophages is crucially dependent on the cytokine IL-10, which is transiently elevated in the peritoneal wash during the early phase of infection. Monocytes from CD45.1 animals transferred early in infection when the IL-10 concentration is high into congenic CD45.2 recipients develop into the MHC IIlo macrophage population. Monocytes transferred later, when the IL-10 concentration has fallen, develop into the MHC IIhi population. In infected IL-10–deficient animals monocytes fail to develop into the MHC IIlo population but can be induced to do so by exogenous application of IL-10. Finally, high numbers of wild-type monocytes injected into IL-10R1–deficient animals develop into MHC IIlo macrophages and were able by a bystander effect to induce the differentiation of the endogenous monocytes to the same fate.

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Coactivation of Syk Kinase and MyD88 Adaptor Protein Pathways by Bacteria Promotes Regulatory Properties of Neutrophils

Cited by 276 publications

References 47 publications

Chromatin remodelling and autocrine TNFα are required for optimal interleukin-6 expression in activated human neutrophils

Chromatin remodelling and autocrine TNFα are required for optimal interleukin-6 expression in activated human neutrophils

IFN‐γ‐producing NKT cells exacerbate sepsis by enhancing C5a generation via IL‐10‐mediated inhibition of CD55 expression on neutrophils

IL-10 Acts As a Developmental Switch Guiding Monocyte Differentiation to Macrophages during a Murine Peritoneal Infection

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