Opposite regulatory effects of IFN-β and IL-3 on C-type lectin receptors, antigen uptake, and phagocytosis in human macrophages

Cardone, Marco; Ikeda, Kyojiro N.; Varano, Barbara; Belardelli, Filippo; Millefiorini, Enrico; Gessani, Sandra; Conti, Lucia

doi:10.1189/jlb.0313168

Cited by 14 publications

(11 citation statements)

References 38 publications

(42 reference statements)

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“…The latter, especially in the absence SHIP, secrete high levels of IL‐4, which in turn induces the alternative activation of macrophages . Recently, it was shown that IL‐3 upregulates CD206 expression on MDM . Although previous studies reported that IL‐3 modulates some functions of monocytes , IL‐3 and GM‐CSF have been used mainly in combination with IL‐4 to differentiate human monocytes into DCs after 5–7 days in culture .…”

Section: Discussionmentioning

confidence: 99%

IL‐3 synergises with basophil‐derived IL‐4 and IL‐13 to promote the alternative activation of human monocytes

et al. 2015

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Basophil-derived IL-4 is involved in the alternative activation of mouse monocytes, as recently shown in vivo. Whether this applies to human basophils and monocytes has not been established yet. Here, we sought to characterize the interaction between basophils and monocytes and identify the molecular determinants. A basophil-monocyte co-culture model revealed that IL-3 and basophil-derived IL-4 and IL-13 induced monocyte production of CCL17, a marker of alternative activation. Critically, IL-3 and IL-4 acted directly on monocytes to induce CCL17 production through histone H3 acetylation, but did not increase the recruitment of STAT5 or STAT6. Although freshly isolated monocytes did not express the IL-3 receptor α chain (CD123), and did not respond to IL-3 (as assessed by STAT5 phosphorylation), the overnight incubation with IL-4 (especially if associated with IL-3) upregulated CD123 expression. IL-3-activated JAK2-STAT5 pathway inhibitors reduced the CCL17 production in response to IL-3 and IL-4, but not to IL-4 alone. Interestingly, monocytes isolated from allergen-sensitized asthmatic patients exhibited a higher expression of CD123. Taken together, our data show that the JAK2-STAT5 pathway modulates both basophil and monocyte effector responses. The coordinated activation of STAT5 and STAT6 may have a major impact on monocyte alternative activation in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

IL‐3 synergises with basophil‐derived IL‐4 and IL‐13 to promote the alternative activation of human monocytes

et al. 2015

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Section: Type I Ifns In Antigen Uptake/processing and T Cell Respomentioning

confidence: 99%

“…Subsequently, we reported that the expression of MR, as well as of the β-glucan receptor CLEC7A/Dectin-1, is comparable in the two DC subtypes [41]. Furthermore, in contrast to other maturation stimuli, IFN-β does not affect the expression of these receptors when used as activation stimulus for IL-4-DCs (Setting 3) [41]. It is worth mentioning that IFN-α and -β strongly down-regulate MR and Dectin-1 expression in human monocyte-derived macrophages and this results in impaired protein antigen endocytosis and pathogen phagocytosis [41].…”

Section: Type I Ifns In Antigen Uptake/processing and T Cell Respomentioning

confidence: 99%

“…Furthermore, in contrast to other maturation stimuli, IFN-β does not affect the expression of these receptors when used as activation stimulus for IL-4-DCs (Setting 3) [41]. It is worth mentioning that IFN-α and -β strongly down-regulate MR and Dectin-1 expression in human monocyte-derived macrophages and this results in impaired protein antigen endocytosis and pathogen phagocytosis [41]. Consistently, infection of alveolar macrophages with influenza A virus has been associated with a marked down-regulation of MR and Dectin-1 mRNA expression as well as of zymosan phagocytosis, concomitantly with a strong type I IFN response [66].…”

Section: Type I Ifns In Antigen Uptake/processing and T Cell Respomentioning

confidence: 99%

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Type I Interferons as Regulators of Human Antigen Presenting Cell Functions

Gessani

Conti

Cornò

et al. 2014

Toxins

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Type I interferons (IFNs) are pleiotropic cytokines, initially described for their antiviral activity. These cytokines exhibit a long record of clinical use in patients with some types of cancer, viral infections and chronic inflammatory diseases. It is now well established that IFN action mostly relies on their ability to modulate host innate and adaptive immune responses. Work in recent years has begun to elucidate the mechanisms by which type I IFNs modify the immune response, and this is now recognized to be due to effects on multiple cell types, including monocytes, dendritic cells (DCs), NK cells, T and B lymphocytes. An ensemble of results from both animal models and in vitro studies emphasized the key role of type I IFNs in the development and function of DCs, suggesting the existence of a natural alliance between these cytokines and DCs in linking innate to adaptive immunity. The identification of IFN signatures in DCs and their dysregulation under pathological conditions will therefore be pivotal to decipher the complexity of this DC-IFN interaction and to better exploit the therapeutic potential of these cells.

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“…Activated DCs link innate to adaptive immunity by secreting immunoregulatory cytokines that polarize CD4 + T helper (Th) cell subsets [4] , [5] . Adaptive and innate lymphocyte subsets in turn modulate DC differentiation and activation through soluble molecules such as interferons (IFNs) or interleukin (IL)-4 and by direct cellular contact [6] – [11] , thus accentuating specific immune responses.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-1 and Interferon-γ Orchestrate β-Glucan-Activated Human Dendritic Cell Programming via IκB-ζ Modulation

Cardone

Dzutsev

et al. 2014

PLoS ONE

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Recognition of microbial components via innate receptors including the C-type lectin receptor Dectin-1, together with the inflammatory environment, programs dendritic cells (DCs) to orchestrate the magnitude and type of adaptive immune responses. The exposure to β-glucan, a known Dectin-1 agonist and component of fungi, yeasts, and certain immune support supplements, activates DCs to induce T helper (Th)17 cells that are essential against fungal pathogens and extracellular bacteria but may trigger inflammatory pathology or autoimmune diseases. However, the exact mechanisms of DC programming by β-glucan have not yet been fully elucidated. Using a gene expression/perturbation approach, we demonstrate that in human DCs β-glucan transcriptionally activates via an interleukin (IL)-1- and inflammasome-mediated positive feedback late-induced genes that bridge innate and adaptive immunity. We report that in addition to its known ability to directly prime T cells toward the Th17 lineage, IL-1 by promoting the transcriptional cofactor inhibitor of κB-ζ (IκB-ζ) also programs β-glucan-exposed DCs to express cell adhesion and migration mediators, antimicrobial molecules, and Th17-polarizing factors. Interferon (IFN)-γ interferes with the IL-1/IκB-ζ axis in β-glucan-activated DCs and promotes T cell-mediated immune responses with increased release of IFN-γ and IL-22, and diminished production of IL-17. Thus, our results identify IL-1 and IFN-γ as regulators of DC programming by β-glucan. These molecular networks provide new insights into the regulation of the Th17 response as well as new targets for the modulation of immune responses to β-glucan-containing microorganisms.

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Opposite regulatory effects of IFN-β and IL-3 on C-type lectin receptors, antigen uptake, and phagocytosis in human macrophages

Cited by 14 publications

References 38 publications

IL‐3 synergises with basophil‐derived IL‐4 and IL‐13 to promote the alternative activation of human monocytes

IL‐3 synergises with basophil‐derived IL‐4 and IL‐13 to promote the alternative activation of human monocytes

Type I Interferons as Regulators of Human Antigen Presenting Cell Functions

Interleukin-1 and Interferon-γ Orchestrate β-Glucan-Activated Human Dendritic Cell Programming via IκB-ζ Modulation

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