Human Monocyte-Derived Dendritic Cells Exposed to Microorganisms Involved in Hypersensitivity Pneumonitis Induce a Th1-Polarized Immune Response

Bellanger, Anne‐Pauline; Pallandre, Jean-René; Borg, Christophe; Sophie, Loeffert; Gbaguidi‐Haore, Houssein; Millon, Laurence

doi:10.1128/cvi.00043-13

Cited by 10 publications

(8 citation statements)

References 34 publications

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“…We were not able to detect IL-17 production by bead-based multiplexed assay in all the conditions tested, but we observed a decrease in the % IL-17 + CD4 + T cells generated with DC ASW as compared to DC CTW . This low percentage of CD4 + T cells producing IL-17, is consistent with reports in the literature 42 and can be explained by the fact that we only used LPS as a stimulus for DC maturation. LPS is known to promote IL-12 production by DCs and thereby to drive mainly Th1 response, whereas LPS alone is a poor inductor of IL-23 43 and therefore of Th17 response.…”

Section: Discussionsupporting

confidence: 92%

<p>Effect of thermal spring water on human dendritic cell inflammatory response</p>

Eliasse

Galliano

Redoulès

et al. 2019

JIR

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Background: Hydrotherapy appears as a valuable therapeutic tool in the management of patients suffering from chronic skin inflammatory diseases. Nevertheless, the underlying immune mechanisms of these beneficial effects remain poorly understood. To better understand the biological effects of thermal spring water on the immune system, we investigated the effects of Avène thermal spring water (ASW) on dendritic cells as key cells participating in the control of the immune response. Methods: Dendritic cells (DCs) were generated from human monocytes and matured with LPS in ASW-based culture medium or in dexamethasone supplemented culture medium as an anti-inflammatory treatment. The phenotypes and abilities of these DCs to produce cytokines and induce allogeneic T cell response was next assessed. Results: We showed that ASW modulated the differentiation of monocytes into DCs and impacted the DC maturation upon LPS priming. We observed a reduction of the CD83, CD86, CD1a and HLA-DR molecule expression and a decrease of IL-12 and IL-23 production whereas IL-10 production was increased. LPS-primed DCs generated in presence of ASW exhibited a reduced capacity to induce naive CD4 + T cell proliferation and IFN-γ and IL-17 production. Conclusion: Our study showed that ASW is endowed with an immunomodulatory potential. ASW limits the DC stimulatory capacity of Th1 and Th17 cell responses by impairing their maturation, IL-12 and IL-23 production and accessory cell function.

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Section: Discussionsupporting

confidence: 92%

<p>Effect of thermal spring water on human dendritic cell inflammatory response</p>

Eliasse

Galliano

Redoulès

et al. 2019

JIR

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“…Pretreatment of cells with doses of 25–100 ng/mL of IL-12 significantly augmented IFN-γ production in comparison to cells with no IL-12 pretreatment ( Fig 1B and S1 Fig ). Interestingly, the doses of IL-12 that altered the responses of human activated CD4 T cells to TCR stimulation (25–100 ng/mL) are similar to the doses used in many other in vitro studies [ 14 , 30 – 33 ] but they are above the concentrations previously described in serum of humans [ 34 – 37 ]. Next, the duration of IL-12 pretreatment required to increase IFN-γ production was examined.…”

Section: Resultsmentioning

confidence: 53%

Exposure of Human CD4 T Cells to IL-12 Results in Enhanced TCR-Induced Cytokine Production, Altered TCR Signaling, and Increased Oxidative Metabolism

et al. 2016

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Human CD4 T cells are constantly exposed to IL-12 during infections and certain autoimmune disorders. The current paradigm is that IL-12 promotes the differentiation of naïve CD4 T cells into Th1 cells, but recent studies suggest IL-12 may play a more complex role in T cell biology. We examined if exposure to IL-12 alters human CD4 T cell responses to subsequent TCR stimulation. We found that IL-12 pretreatment increased TCR-induced IFN-γ, TNF-α, IL-13, IL-4 and IL-10 production. This suggests that prior exposure to IL-12 potentiates the TCR-induced release of a range of cytokines. We observed that IL-12 mediated its effects through both transcriptional and post-transcriptional mechanisms. IL-12 pretreatment increased the phosphorylation of AKT, p38 and LCK following TCR stimulation without altering other TCR signaling molecules, potentially mediating the increase in transcription of cytokines. In addition, the IL-12-mediated enhancement of cytokines that are not transcriptionally regulated was partially driven by increased oxidative metabolism. Our data uncover a novel function of IL-12 in human CD4 T cells; specifically, it enhances the release of a range of cytokines potentially by altering TCR signaling pathways and by enhancing oxidative metabolism.

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“…These data suggest that fungi that expose low levels of β-glucans at their surface are more susceptible to induce allergic Th2 polarized immune responses. In agreement, β-glucans from Wallemia sebi and Eurotium amstelodami, fungal species associated to HP development, promote Th1 polarized responses by DCs [20]. Along with a primordial role for dectin-1 in antifungal defences, mutations in dectin-1 and CARD9 have been associated with fungal infections [46][47][48].…”

Section: Pathogen-associated Molecular Patterns and Pattern-recognitimentioning

confidence: 82%

“…DCs are particularly well equipped to decipher the fine structure of fungi, and the extreme plasticity of their response shapes the development of naïve CD4+ T cells into Th1, Th2 or Th17 cells that differentially affect antifungal responses [19]. For example, DCs exposed to Eurotium amstelodami or Wallemi sebi, two filamentous fungi involved in HP, induce a Th1 polarized pathogenic response [20], whereas DCs exposed to Alternaria alternata, a common allergenic fungi responsible of asthma, trigger a potent Th2 skewed immune response [21].…”

Section: Processing Of Fungal Particles In the Airwaysmentioning

confidence: 99%

Immune responses to airborne fungi and non-invasive airway diseases

2014

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Inhalation of fungal particles is a ubiquitous way of exposure to microorganisms during human life; however, this exposure may promote or exacerbate respiratory diseases only in particular exposure conditions and human genetic background. Depending on the fungal species and form, fungal particles can induce symptoms in the lung by acting as irritants, aeroallergens or pathogens causing infection. Some thermophilic species can even act in all these three ways (e.g. Aspergillus, Penicillium), mesophilic species being only involved in allergic and/or non-allergic airway diseases (e.g. Cladosporium, Alternaria, Fusarium). The goal of the present review is to present the current knowledge on the interaction between airborne fungal particles and the host immune system, to illustrate the differences of immune sensing of different fungal species and to emphasise the importance of conducting research on non-conventional mesophilic fungal species. Indeed, the diversity of fungal species we inhale and the complexity of their composition have a direct impact on fungal particle recognition and immune system decision to tolerate or respond to those particles, eventually leading to collateral damages promoting airway pathologies.

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Human Monocyte-Derived Dendritic Cells Exposed to Microorganisms Involved in Hypersensitivity Pneumonitis Induce a Th1-Polarized Immune Response

Cited by 10 publications

References 34 publications

<p>Effect of thermal spring water on human dendritic cell inflammatory response</p>

<p>Effect of thermal spring water on human dendritic cell inflammatory response</p>

Exposure of Human CD4 T Cells to IL-12 Results in Enhanced TCR-Induced Cytokine Production, Altered TCR Signaling, and Increased Oxidative Metabolism

Immune responses to airborne fungi and non-invasive airway diseases

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