Dendritic cells from X-linked hyper-IgM patients present impaired responses to Candida albicans and Paracoccidioides brasiliensis Otavio Cabral Marques,

Slides:

Advertisements

Similar presentations

Monica G. Lawrence, MD, Jennifer W. Leiding, MD, Jonathan J

Advertisements

Impaired TH17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy

Defective calcium signaling and disrupted CD20–B-cell receptor dissociation in patients with common variable immunodeficiency disorders Annick A.J.M.

Correlation of allergen-specific T follicular helper cell counts with specific IgE levels and efficacy of allergen immunotherapy Yin Yao, MD, Cai-Ling.

Induction of anergic allergen-specific suppressor T cells using tolerogenic dendritic cells derived from children with allergies to house dust mites

Ambient particulate matter directs nonclassic dendritic cell activation and a mixed TH1/TH2-like cytokine response by naive CD4+ T cells Marc A. Williams,

William A. Comrie, PhD, Aiman J

Human CD40 ligand deficiency dysregulates the macrophage transcriptome causing functional defects that are improved by exogenous IFN-γ Otavio Cabral-Marques,

Human TH17 cell development requires processing of dendritic cell–derived CXCL8 by neutrophil elastase Yuri Souwer, PhD, Tom Groot Kormelink, PhD, Esther.

Impaired TH17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy

IgE cross-linking impairs monocyte antiviral responses and inhibits influenza-driven TH1 differentiation Regina K. Rowe, MD, PhD, David M. Pyle, MD,

Sytze de Roock, PhD, Arie J

Reduced IFN-γ receptor expression and attenuated IFN-γ response by dendritic cells in patients with atopic dermatitis Eva Gros, MSc, Susanne Petzold,

Human B cells promote T-cell plasticity to optimize antibody response by inducing coexpression of TH1/TFH signatures Jelle de Wit, PhD, Tineke Jorritsma,

Bruton tyrosine kinase mediates TLR9-dependent human dendritic cell activation Vassilios Lougaris, MD, Manuela Baronio, PhD, Massimiliano Vitali, PhD,

T-cell regulation during viral and nonviral asthma exacerbations

Penicillium marneffei infection and impaired IFN-γ immunity in humans with autosomal- dominant gain-of-phosphorylation STAT1 mutations Pamela P.W. Lee,

Anti–IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL- 5 and IL-5 receptor levels Miguel L. Stein, MD, Joyce M. Villanueva,

Targeting Toll-like receptors on dendritic cells modifies the TH2 response to peanut allergens in vitro Pierre Pochard, PhD, Brian Vickery, MD, M. Cecilia.

Imidazoquinoline Toll-like receptor 8 agonists activate human newborn monocytes and dendritic cells through adenosine-refractory and caspase-1–dependent.

Imidazoquinoline Toll-like receptor 8 agonists activate human newborn monocytes and dendritic cells through adenosine-refractory and caspase-1–dependent.

Glucocorticoids promote intrinsic human TH17 differentiation

Triggering of specific Toll-like receptors and proinflammatory cytokines breaks allergen- specific T-cell tolerance in human tonsils and peripheral blood

CD19 controls Toll-like receptor 9 responses in human B cells

Susan L. Prescott, PhD, MD, Paul Noakes, BSc (Hons), PhD, Bonita W. Y

Human dendritic cell subset 4 (DC4) correlates to a subset of CD14dim/−CD16++ monocytes Federica Calzetti, BS, Nicola Tamassia, PhD, Alessandra Micheletti,

Clara cell 16-kd protein downregulates TH2 differentiation of human naive neonatal T cells Sofi Johansson, MSc, Göran Wennergren, MD, PhD, Nils Åberg,

Decreased T-cell receptor signaling through CARD11 differentially compromises forkhead box protein 3–positive regulatory versus TH2 effector cells to.

Langerhans Cells from Human Cutaneous Squamous Cell Carcinoma Induce Strong Type 1 Immunity Hideki Fujita, Mayte Suárez-Fariñas, Hiroshi Mitsui, Juana.

CD94/NKG2C is a killer effector molecule in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis Esther Morel, PhD, Salvador Escamochero,

Signaling impairments in maternal T cells engrafted in an infant with a novel IL-2 receptor γ mutation Aaruni Khanolkar, MBBS, PhD, Jeffrey D. Wilks,

Mark Gorelik, MD, Satya D. Narisety, MD, Anthony L

Interleukin receptor-associated kinase-4 deficiency impairs Toll-like receptor–dependent innate antiviral immune responses Douglas R. McDonald, MD, PhD,

Human mast cells drive memory CD4+ T cells toward an inflammatory IL-22+ phenotype Nicolas Gaudenzio, PhD, Camille Laurent, MD, Salvatore Valitutti,

Expression of FcɛRI on dendritic cell subsets in peripheral blood of patients with atopic dermatitis and allergic asthma Inge M.J. Beeren, MSc, Marjolein.

Davide Pennino, MSc, Pankaj K

Human CD40 ligand deficiency dysregulates the macrophage transcriptome causing functional defects that are improved by exogenous IFN-γ Otavio Cabral-Marques,

Targeting allergen to FcγRI reveals a novel TH2 regulatory pathway linked to thymic stromal lymphopoietin receptor Kathryn E. Hulse, PhD, Amanda J. Reefer,

Bet v 1–specific T-cell receptor/forkhead box protein 3 transgenic T cells suppress Bet v 1–specific T-cell effector function in an activation-dependent.

IL-17 in atopic eczema: Linking allergen-specific adaptive and microbial-triggered innate immune response Kilian Eyerich, MD, Davide Pennino, PhD, Claudia.

Peanut-specific type 1 regulatory T cells induced in vitro from allergic subjects are functionally impaired Laurence Pellerin, PhD, Jennifer Anne Jenks,

Role of B cells in TH cell responses in a mouse model of asthma

Streptococcus pyogenes–induced cutaneous lymphocyte antigen–positive T cell– dependent epidermal cell activation triggers TH17 responses in patients with.

Baricitinib treatment in a patient with a gain-of-function mutation in signal transducer and activator of transcription 1 (STAT1) Kornvalee Meesilpavikkai,

Histamine receptor 2 is a key influence in immune responses to intestinal histamine- secreting microbes Ruth Ferstl, PhD, Remo Frei, PhD, Elisa Schiavi,

The mannose receptor negatively modulates the Toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2,3-dioxygenase axis in dendritic cells affecting.

Myeloid and plasmacytoid dendritic cells in induced sputum after allergen inhalation in subjects with asthma Benny Dua, MSc, Richard M. Watson, BSc,

The L412F variant of Toll-like receptor 3 (TLR3) is associated with cutaneous candidiasis, increased susceptibility to cytomegalovirus, and autoimmunity

Liam O’Mahony, PhD, Mübeccel Akdis, MD, PhD, Cezmi A. Akdis, MD

Monica G. Lawrence, MD, Jennifer W. Leiding, MD, Jonathan J

A novel hypomorphic mutation in STIM1 results in a late-onset immunodeficiency Heidi Schaballie, MD, Rémy Rodriguez, MS, Emmanuel Martin, PhD, Leen Moens,

Sara Paveglio, PhD, MS, Erin Bennett, MS, Kelly L. Hawley, PhD, Adam P

Influence of cytomegalovirus infection on immune cell phenotypes in patients with common variable immunodeficiency Sayed Mahdi Marashi, PhD, Mohammed.

Inhibition of human allergic T-cell responses by IL-10–treated dendritic cells: Differences from hydrocortisone-treated dendritic cells Iris Bellinghausen,

Angelic M. G. van der Aar, PhD, Darya S

The mannose receptor negatively modulates the Toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2,3-dioxygenase axis in dendritic cells affecting.

Defective calcium signaling and disrupted CD20–B-cell receptor dissociation in patients with common variable immunodeficiency disorders Annick A.J.M.

Reply Journal of Allergy and Clinical Immunology

IL-10–producing monocytes differentiate to alternatively activated macrophages and are increased in atopic patients Antje Prasse, MD, Martin Germann,

Human basophils may not undergo modulation by DC-SIGN and mannose receptor– targeting immunotherapies due to absence of receptors Mrinmoy Das, MSc, Caroline.

Immune pathomechanism of drug hypersensitivity reactions

Cigarette smoke exposure is associated with vitamin D3 deficiencies in patients with chronic rhinosinusitis Jennifer K. Mulligan, PhD, Whitney Nagel,

Janet Chou, MD, Maxim Lutskiy, MD, PhD, Erdyni Tsitsikov, PhD, Luigi D

Neuropeptide signaling through neurokinin-1 and neurokinin-2 receptors augments antigen presentation by human dendritic cells Junya Ohtake, PhD, Shun.

IgG4 production is confined to human IL-10–producing regulatory B cells that suppress antigen-specific immune responses Willem van de Veen, MSc, Barbara.

Hydroxychloroquine preferentially induces apoptosis of CD45RO+ effector T cells by inhibiting autophagy: A possible mechanism for therapeutic modulation.

Early-onset inflammatory bowel disease and common variable immunodeficiency–like disease caused by IL-21 deficiency Elisabeth Salzer, MD, Aydan Kansu,

Natural history of cow’s milk allergy

Perturbations of natural killer cell regulatory functions in respiratory allergic diseases Francesca Scordamaglia, MD, Mirna Balsamo, PhD, Antonio Scordamaglia,

Induction of anergic allergen-specific suppressor T cells using tolerogenic dendritic cells derived from children with allergies to house dust mites

Presentation transcript:

Dendritic cells from X-linked hyper-IgM patients present impaired responses to Candida albicans and Paracoccidioides brasiliensis Otavio Cabral Marques, MSc, Christina Arslanian, BSc, Rodrigo Nalio Ramos, MSc, Mariana Morato, MSc, LenaFriederike Schimke, MD, Paulo Vitor Soeiro Pereira, MSc, Sonia Jancar, MD, PhD, Janaíra Fernandes Ferreira, MD, Cristina Worm Weber, MD, Gisele Kuntze, MD, Nelson Augusto Rosario-Filho, MD, PhD, Beatriz Tavares Costa Carvalho, MD, Patricia Cruz Bergami-Santos, PhD, Mary J. Hackett, BSc, Hans D. Ochs, MD, Troy R. Torgerson, MD, PhD, Jose Alexandre Marzagão Barbuto, MD, PhD, Antonio Condino-Neto, MD, PhD Journal of Allergy and Clinical Immunology Volume 129, Issue 3, Pages 778-786 (March 2012) DOI: 10.1016/j.jaci.2011.10.026 Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Normal expression and secretion of pattern recognition receptors by iDCs from patients with X-HIGM. Flow cytometric analysis of iDCs derived from peripheral blood monocytes (PBMs) in the presence of GM-CSF and IL-4 showed the expected CD14 downregulation (A). X-HIGM iDCs demonstrate normal expression of TLR2 and TLR4 (B) and secrete normal amounts of PTX3 compared with normal controls (C) (P < .05; n = 5, Mann-Whitney test). MFI, Mean fluorescence intensity. Journal of Allergy and Clinical Immunology 2012 129, 778-786DOI: (10.1016/j.jaci.2011.10.026) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 DCs from CD40L-deficient patients express reduced CD80, CD86, and HLA-DR levels that can be restored to normal levels by stimulation with sCD40L. Flow cytometric analysis of iDCs showing that cells from patients with X-HIGM express reduced levels of HLA-DR, CD80, and CD86 (A and B). mDCs incubated with sCD40L show expression of costimulatory and HLA-DR molecules at levels similar to those in normal controls (Fig 2, A and B). mDCs incubated with C albicans and P brasiliensis exhibit reduced expression of HLA-DR and CD80 but normal levels of CD86 (C) relative to normal controls. Significant differences are denoted by asterisk (P < .05; n = 5, Mann-Whitney test). MFI, Mean fluorescence intensity. Journal of Allergy and Clinical Immunology 2012 129, 778-786DOI: (10.1016/j.jaci.2011.10.026) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 DCs from CD40L-deficient patients induced normal TH17 cell generation. Patients with X-HIGM showed a percentage of TH17 cells similar to that in normal controls after stimulation of T cells with iDCs, phorbol 12-myristate 13-acetate plus ionomycin, or C albicans–pulsed mDCs (A). The levels of IL-17 in cocultures of T cells with C albicans– or P brasiliensis–pulsed mDCs from patients with X-HIGM were also similar to those of normal controls (B) (P > .05 in all situations; n = 5, Mann-Whitney test). PMA, Phorbol 12-myristate 13-acetate. Journal of Allergy and Clinical Immunology 2012 129, 778-786DOI: (10.1016/j.jaci.2011.10.026) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 IL-12 and IL-10 production by X-HIGM mDCs. mDCs from patients with X-HIGM secrete decreased IL-12 but increased IL-10 in response to P brasiliensis and C albicans. After sCD40L stimulation of X-HIGM mDCs, IL-12 and IL-10 secretions were restored to a pattern similar to that observed in healthy controls (A and B). Significant differences are denoted by asterisk (P < .05; n = 5, Mann-Whitney test). Journal of Allergy and Clinical Immunology 2012 129, 778-786DOI: (10.1016/j.jaci.2011.10.026) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 X-HIGM DCs induce normal CD4+ and CD8+ T-cell proliferation in coculture. iDCs and P brasiliensis– or C albicans–pulsed mDCs from patients with X-HIGM (blue) showed a normal capacity to induce CD4+ and CD8+ T-cell proliferation compared with healthy control cells (red) (A and B) (P > .05 in all situations; n = 5, Mann-Whitney test). CFSE, 5,6-Carboxyfluorescein diacetate succinimidyl ester. Journal of Allergy and Clinical Immunology 2012 129, 778-786DOI: (10.1016/j.jaci.2011.10.026) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 In cocultures, mDCs from CD40L-deficient patients skew T-cell response to a TH2 pattern. Lower levels of IFN-γ and higher IL-4 and IL-5 production (A-C) were detected in cells from patients with X-HIGM. This was reversed to a pattern similar to that in normal controls when X-HIGM mDCs were matured in the presence of sCD40L. Significant differences are denoted by asterisk (P < .05; n = 5, Mann-Whitney test). Journal of Allergy and Clinical Immunology 2012 129, 778-786DOI: (10.1016/j.jaci.2011.10.026) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 7 The imbalanced production of IFN-γ and IL-4 is reversed by exogenous sCD40L. Supernatants of T cells cocultured with C albicans–pulsed mDCs from patients with X-HIGM showed reduced level of IFN-γ, which was upregulated by exogenous sCD40L (A), while increased level of IL-4 was downregulated (B). Significant differences are denoted by asterisk (P < .05; n = 5, Mann-Whitney test). Journal of Allergy and Clinical Immunology 2012 129, 778-786DOI: (10.1016/j.jaci.2011.10.026) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions