Neutrophils in antiretroviral therapy–controlled HIV demonstrate hyperactivation associated with a specific IL-17/IL-22 environment Laure Campillo-Gimenez,

Slides:

Advertisements

Similar presentations

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

Advertisements

Vitamin D3 treatment of vitamin D–insufficient asthmatic patients does not alter immune cell function Brandy Reid, MS, Pierre-Olivier Girodet, MD, PhD,

Barbara Stanic, PhD, Willem van de Veen, PhD, Oliver F

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

Topical application of a vitamin D3 analogue and corticosteroid to psoriasis plaques decreases skin infiltration of TH17 cells and their ex vivo expansion

Flow cytometry imaging identifies rare TH2 cells expressing thymic stromal lymphopoietin receptor in a “proallergic” milieu Amanda J. Reefer, MS, Kathryn.

The importance of being “pure” neutrophils

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

Reduced TH1/TH17 CD4 T-cell numbers are associated with impaired purified protein derivative–specific cytokine responses in patients with HIV-1 infection

Cell-to-cell contact between activated CD4+ T lymphocytes and unprimed monocytes interferes with a TH1 response Miriam Wittmann, MD, Mareike Alter, Tanja.

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,

CD4+ T cells in patients with chronic inflammatory rheumatic disorders show distinct levels of exhaustion Theresa Frenz, PhD, Elena Grabski, PhD, Daniela.

IL-10 disrupts the Brd4-docking sites to inhibit LPS-induced CXCL8 and TNF-α expression in monocytes: Implications for chronic obstructive pulmonary disease

Maternal house dust mite exposure during pregnancy enhances severity of house dust mite–induced asthma in murine offspring Phoebe K. Richgels, MS, Amnah.

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,

FOXP3+ CD4 T-cell maturity and responses to microbial stimulation alter with age and associate with early-life gut colonization Sophia Björkander, Maria.

Topical application of a vitamin D3 analogue and corticosteroid to psoriasis plaques decreases skin infiltration of TH17 cells and their ex vivo expansion

Infliximab induces downregulation of the IL-12/IL-23 axis in 6-sulfo-LacNac (slan)+ dendritic cells and macrophages Patrick M. Brunner, MD, Frieder Koszik,

Identification of a distinct glucocorticosteroid-insensitive pulmonary macrophage phenotype in patients with chronic obstructive pulmonary disease Kirandeep.

Type 3 innate lymphoid cells induce proliferation of CD94+ natural killer cells Shuo Li, PhD, Hideaki Morita, MD, PhD, Beate Rückert, Sci Tec, Tadech.

IL-2 consumption by highly activated CD8 T cells induces regulatory T-cell dysfunction in patients with hemophagocytic lymphohistiocytosis Stéphanie.

Responsiveness to respiratory syncytial virus in neonates is mediated through thymic stromal lymphopoietin and OX40 ligand Junyan Han, PhD, Azzeddine.

Toll-like receptor 4 ligation enforces tolerogenic properties of oral mucosal Langerhans cells Jean-Pierre Allam, MD, Wen-Ming Peng, MSc, Torsten Appel,

Lung T-cell responses to nontypeable Haemophilus influenzae in patients with chronic obstructive pulmonary disease Paul T. King, MD, PhD, Steven Lim,

Selective and direct activation of human neutrophils but not eosinophils by Toll-like receptor 8 Markus Janke, PhD, Jens Poth, Vera Wimmenauer, Thomas.

Glucocorticoids promote intrinsic human TH17 differentiation

Identification of a distinct glucocorticosteroid-insensitive pulmonary macrophage phenotype in patients with chronic obstructive pulmonary disease Kirandeep.

Flow cytometric measurement of STAT1 and STAT3 phosphorylation in CD4+ and CD8+ T cells—clinical applications in primary immunodeficiency diagnostics

Dawn C. Newcomb, PhD, Madison G

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

Vitamin D3 treatment of vitamin D–insufficient asthmatic patients does not alter immune cell function Brandy Reid, MS, Pierre-Olivier Girodet, MD, PhD,

Kathleen R. Bartemes, BA, Gail M. Kephart, BS, Stephanie J

Thymic stromal lymphopoietin activation of basophils in patients with allergic asthma is IL-3 dependent Brittany M. Salter, BSc, John Paul Oliveria,

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

Differential expression of functional chemokine receptors on human blood and lung group 2 innate lymphoid cells Cathryn A. Weston, PhD, Batika M.J. Rana,

Katherine G. MacDonald, BSc, Nicholas A. J

Thymic stromal lymphopoietin converts human epidermal Langerhans cells into antigen- presenting cells that induce proallergic T cells Susanne Ebner, PhD,

David M. Pyle, BS, Victoria S. Yang, MD, Rebecca S

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

Corticosteroid-resistant asthma is associated with classical antimicrobial activation of airway macrophages Elena Goleva, PhD, Pia J. Hauk, MD, Clifton.

Targeting Fel d 1 to FcγRI induces a novel variation of the TH2 response in subjects with cat allergy Kathryn E. Hulse, BS, Amanda J. Reefer, MS, Victor.

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

Inhibition of angiogenesis by IL-32: Possible role in asthma

Chronic cat allergen exposure induces a TH2 cell–dependent IgG4 response related to low sensitization Amedee Renand, PhD, Luis D. Archila, MSc, John.

Role of hyaluronan and hyaluronan-binding proteins in human asthma

Brent E. Palmer, PhD, Douglas G. Mack, PhD, Allison K

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.

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

Jill A. Poole, MD, Neil E. Alexis, PhD, Conrad Parks, BS, Amy K

Mammalian target of rapamycin inhibition counterbalances the inflammatory status of immune cells in patients with chronic granulomatous disease Aurélie.

Impact of immunotherapy on blood dendritic cells in patients with Hymenoptera venom allergy Katharina Dreschler, Kai Bratke, PhD, Sebastian Petermann,

Prostaglandin E2 resistance in granulocytes from patients with aspirin-exacerbated respiratory disease Tanya M. Laidlaw, MD, Anya J. Cutler, Molly S.

Staphylococcal exotoxins are strong inducers of IL-22: A potential role in atopic dermatitis Margarete Niebuhr, MD, Helena Scharonow, MS, Merle Gathmann,

IL-17E upregulates the expression of proinflammatory cytokines in lung fibroblasts Séverine Létuvé, PhD, Stéphane Lajoie-Kadoch, MSc, Séverine Audusseau,

Amplification of Toll-like receptor–mediated signaling through spleen tyrosine kinase in human B-cell activation Shigeru Iwata, MD, PhD, Kunihiro Yamaoka,

Persistence of natural killer cells with expansion of a hypofunctional CD56−CD16+KIR+NKG2C+ subset in a patient with atypical Janus kinase 3–deficient.

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

Eosinophilic gastrointestinal disease and peanut allergy are alternatively associated with IL-5+ and IL-5− TH2 responses Calman Prussin, MD, Joohee Lee,

Duy Pham, PhD, Sarita Sehra, PhD, Xin Sun, PhD, Mark H. Kaplan, PhD

CCL17/thymus and activation-regulated chemokine induces calcitonin gene–related peptide in human airway epithelial cells through CCR4 Kandace Bonner,

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

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

Innate immune defects correlate with failure of antibody responses to H1N1/09 vaccine in HIV-infected patients Suresh Pallikkuth, PhD, Sudheesh Pilakka.

Thymic stromal lymphopoietin does not activate human basophils

Intact IL-12 signaling is necessary for the generation of human natural killer cells with enhanced effector function after restimulation Venkateswara.

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

CCL17/thymus and activation-regulated chemokine induces calcitonin gene–related peptide in human airway epithelial cells through CCR4 Kandace Bonner,

Invariant natural killer T cells from children with versus without food allergy exhibit differential responsiveness to milk-derived sphingomyelin Soma.

Presentation transcript:

Neutrophils in antiretroviral therapy–controlled HIV demonstrate hyperactivation associated with a specific IL-17/IL-22 environment Laure Campillo-Gimenez, PhD, Sarah Casulli, PhD, Yasmine Dudoit, MS, Sophie Seang, MD, Guislaine Carcelain, MD, PhD, Sidonie Lambert-Niclot, PharmD, PhD, Victor Appay, PhD, Brigitte Autran, MD, PhD, Roland Tubiana, MD, Carole Elbim, MD, PhD Journal of Allergy and Clinical Immunology Volume 134, Issue 5, Pages 1142-1152.e5 (November 2014) DOI: 10.1016/j.jaci.2014.05.040 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Highly activated circulating PMNs from HIV-infected patients. A and B, Expression of cell-surface molecules on resting PMNs was studied on whole-blood samples maintained at 4°C. One histogram representative of CD62L, CD11b, and CD16b expression at the surface of PMNs from HCs (black) and HIV-infected patients (white) is shown; the isotype control is shown in gray (Fig 1, A). Average mean fluorescence intensity (MFI) in each group is shown in Fig 1, B. C, Production of ROS by unstimulated PMNs. D, Spontaneous PMN death was measured by incubating whole-blood samples with PBS for 20 hours at 37°C; results are expressed as percentages of apoptotic (left) and necrotic (right) PMNs. *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology 2014 134, 1142-1152.e5DOI: (10.1016/j.jaci.2014.05.040) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Lack of monocyte activation in HIV-infected patients. A, Surface expression of CD44 and CD11b on monocytes was evaluated as mean fluorescence intensity (MFI) on total CD14+ cells; HLA-DR expression on monocytes was estimated by the percentage of CD14+ cells that highly expressed HLA-DR. B, Serum level of sCD14. C, Average percentages of classical, intermediate, and proinflammatory monocytes among total CD14+ cells in each group. D, Percentage of proinflammatory monocytes that expressed the MDC-8 marker. E, ROS production by unstimulated monocytes. Journal of Allergy and Clinical Immunology 2014 134, 1142-1152.e5DOI: (10.1016/j.jaci.2014.05.040) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Higher level of PMN activation in HIV-infected patients with a history of inflammatory diseases than in the HIV-infected patients without inflammatory diseases. A, Expression of cell-surface molecules (CD62L, CD11b, and CD16b) on resting PMNs. B, ROS production by unstimulated PMNs. C, Percentages of apoptotic and necrotic PMNs. All measurements were made in HCs and patients from the HIV(I) and HIV(NI) groups. *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology 2014 134, 1142-1152.e5DOI: (10.1016/j.jaci.2014.05.040) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Similar level of monocyte and T-cell activation in HIV-infected patients with a history of inflammatory diseases and HIV-infected patients without inflammatory diseases. A-D, CD44, CD11b, and HLA-DR expression on monocytes (Fig 4, A); serum level of sCD14 (Fig 4, B); ROS production by unstimulated monocytes (Fig 4, C); and percentages of proinflammatory monocytes that expressed the MDC-8 marker (Fig 4, D). E and F, Percentage of memory CD3+CD8+ cells (left) or CD3+CD4+ cells (right) that expressed both CD38 and HLA-DR (Fig 4, E) or CD57 (Fig 4, F) markers. All measurements were made in HCs and patients in the HIV(I) and HIV(NI) groups. **P < .01 and ***P < .001. Journal of Allergy and Clinical Immunology 2014 134, 1142-1152.e5DOI: (10.1016/j.jaci.2014.05.040) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Specific cytokine environment in HIV-infected patients. A-C, Serum levels of IL-18 (left), TGF-β (middle), and IL-22 (right; Fig 5, A) and percentages of total IL-17+ (Fig 5, B) and IL-22+ (Fig 5, C) cells in HCs (n = 22) and HIV-infected patients (n = 60). D-F, Percentage of IL-17+ (Fig 5, D) or IL-22+ (Fig 5, E) cells among PBMCs and serum IL-22 concentration (Fig 5, F) in HCs and patients in the HIV(I) and HIV(NI) groups. G, Correlation between the percentage of total IL-17+ cells and CD11b (left) or CD62L (middle) expression on resting PMNs and ROS production by unstimulated PMNs (right). *P < .05 and **P < .01. Journal of Allergy and Clinical Immunology 2014 134, 1142-1152.e5DOI: (10.1016/j.jaci.2014.05.040) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Model for HIV-associated PMN hyperactivation. HIV-1 activates the inflammasome, leading to production of IL-18, which, combined with TGF-β, plays a role in the expansion of IL-17–producing cells. IL-17 production in tissue leads to IL-8 secretion by endothelial cells, which in turn induces massive recruitment and activation of PMNs. IL-18 might also activate PMNs directly; this in turn might produce IL-18. Cytotoxic contents released by activated and necrotic PMNs lead to tissue injury. Vascular and tissue lesions might be counteracted by IL-22, depending on the level of this cytokine. Journal of Allergy and Clinical Immunology 2014 134, 1142-1152.e5DOI: (10.1016/j.jaci.2014.05.040) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Normal functional capacities of PMNs from HIV-infected patients depending on the agonist. A and B, CD62L (Fig E1, A) and CD11b (Fig E1, B) expression on the PMN surface was measured after incubation of whole-blood samples for 45 minutes with PBS, TLR1/2 agonist, TLR4 agonist, or TNF-α. C, ROS production by PMNs was measured after pretreatment of whole-blood samples for 45 minutes with PBS, TLR1/2 agonist, TLR4 agonist, or TNF and stimulation for 5 minutes with formyl-methionyl-leucyl-phenylalanine (fMLP). D, PMN survival was analyzed by incubating whole-blood samples with PBS, TLR1/2 agonist, or TLR4 agonist for 20 hours at 37°C; the percentage of apoptotic PMNs was determined, as described in the legend of Fig 1. All measurements were taken in HCs and HIV-infected patients. Values are means ± SEMs. ***P < .001. Journal of Allergy and Clinical Immunology 2014 134, 1142-1152.e5DOI: (10.1016/j.jaci.2014.05.040) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Levels of T-cell activation and immunosenescence. A, Percentage of memory CD3+CD8+ (upper panel) or CD3+CD4+ (lower panel) cells that express both CD38 and HLA-DR markers. B, Percentage of memory CD3+CD8+ (upper panel) or CD3+CD4+ (lower panel) cells that express the CD57 marker. Memory cells were defined by means of Boolean gating with Kaluza Software (CD4+ or CD8+ and not naive cells). C, Correlation between markers of T-lymphocyte activation and T-lymphocyte immunosenescence. Journal of Allergy and Clinical Immunology 2014 134, 1142-1152.e5DOI: (10.1016/j.jaci.2014.05.040) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Cytokine quantification in HIV-infected patients. Multiple cytokines and chemokines were quantified in serum from HCs and HIV-infected patients. IL-23, IL-21, and IL-1β levels were measured by means of ELISA, whereas IL-17A/F, monocyte chemoattractant protein 1 (MCP-1), IL-8, IL-6, TNF-α, IL-10, IFN-α, and GM-CSF were detected by using the Cytometric Bead Array. *P < .05. Journal of Allergy and Clinical Immunology 2014 134, 1142-1152.e5DOI: (10.1016/j.jaci.2014.05.040) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Intracellular cytokine analysis. A, Gating process. Cells were first gated on the basis of forward-scatter (FS) and side-scatter (SS) characteristics (gate A). Then only singlets (gate B) and live cells (defined by the Fixable Viability marker eF450) were included in the analysis. B, Representative dot plots of IL-17+ cells after incubation without (NS) or with staphylococcal enterotoxin B (SEB) in 1 HC and one HIV-infected patient. The negative control used isotype fluorochrome-conjugated antibodies (Iso) corresponding to anti–IL-17 fluorochrome-conjugated antibody. C, Percentage of total IL-17+ (left) and IL-22+ (right) cells among PBMCs after SEB stimulation in HC and HIV-infected patients with (HIV[I]) or without (HIV[NI]) inflammatory diseases. D, After gating on total IL-17+ or IL-22+ cells, phenotype analyses were performed. We used the expression of CD3 and CD4 markers to define T helper cells, the CD14 marker to define monocytes, and the iNKT (TCRVα24-Vβ11) and Tγδ (TCRγδ) markers. Each selected dot plot represents 1 HIV-infected patient. Journal of Allergy and Clinical Immunology 2014 134, 1142-1152.e5DOI: (10.1016/j.jaci.2014.05.040) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions