scholarly journals Complement Component 3C3 and C3a Receptor Are Required in Chitin-Dependent Allergic Sensitization to Aspergillus fumigatus but Dispensable in Chitin-Induced Innate Allergic Inflammation

mBio ◽  
2013 ◽  
Vol 4 (2) ◽  
Author(s):  
René M. Roy ◽  
Hugo C. Paes ◽  
Som G. Nanjappa ◽  
Ron Sorkness ◽  
David Gasper ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Wall ◽  
Dendritic Cells ◽  
Aspergillus Fumigatus ◽  
Critical Role ◽  
Allergic Sensitization ◽  
Allergic Inflammation ◽  
Intratracheal Administration ◽  
Fungal Allergens ◽  
Anaphylatoxin C3a

ABSTRACT Levels of the anaphylatoxin C3a are increased in patients with asthma compared with those in nonasthmatics and increase further still during asthma exacerbations. However, the role of C3a during sensitization to allergen is poorly understood. Sensitization to fungal allergens, such as Aspergillus fumigatus, is a strong risk factor for the development of asthma. Exposure to chitin, a structural polysaccharide of the fungal cell wall, induces innate allergic inflammation and may promote sensitization to fungal allergens. Here, we found that coincubation of chitin with serum or intratracheal administration of chitin in mice resulted in the generation of C3a. We established a model of chitin-dependent sensitization to soluble Aspergillus antigens to test the contribution of complement to these events. C3−/− and C3aR−/− mice were protected from chitin-dependent sensitization to Aspergillus and had reduced lung eosinophilia and type 2 cytokines and serum IgE. In contrast, complement-deficient mice were not protected against chitin-induced innate allergic inflammation. In sensitized mice, plasmacytoid dendritic cells from complement-deficient animals acquired a tolerogenic profile associated with enhanced regulatory T cell responses and suppressed Th2 and Th17 responses specific for Aspergillus. Thus, chitin induces the generation of C3a in the lung, and chitin-dependent allergic sensitization to Aspergillus requires C3aR signaling, which suppresses regulatory dendritic cells and T cells and induces allergy-promoting T cells. IMPORTANCE Asthma is one of the fastest growing chronic illnesses worldwide. Chitin, a ubiquitous polymer in our environment and a key component in the cell wall of fungal spores and the exoskeletons of insects, parasites, and crustaceans, triggers innate allergic inflammation. However, there is little understanding of how chitin is initially recognized by mammals and how early recognition of chitin affects sensitization to environmental allergens and development of allergic asthma. The complement system is evolutionarily one of the oldest facets of the early or innate warning systems in mammals. We studied whether and how complement components influence the recognition of chitin and shape the downstream sensitization toward fungal allergens. We show here that complement recognition of chitin plays a critical role in shaping the behavior of dendritic cells, which in turn regulate the function of T cells that mediate allergic responses to fungi.

scholarly journals CpG-ODN Signaling via Dendritic Cells-Expressing MyD88, but Not IL-10, Inhibits Allergic Sensitization

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 743
Author(s):  
Ricardo Wesley Alberca ◽  
Eliane Gomes ◽  
Momtchilo Russo
Keyword(s):  
Dendritic Cells ◽  
Allergic Sensitization ◽  
Allergic Inflammation ◽  
Allergen Challenge ◽  
Lavage Fluid ◽  
Specific Cell ◽  
Cpg Odn ◽  
Allergic Lung Disease ◽  
Myd88 Pathway

Allergen-specific T helper (Th)2 cells orchestrate upon allergen challenge the development of allergic eosinophilic lung inflammation. Sensitization with alum adjuvant, a type 2 adjuvant, has been used extensively in animal models of allergic lung disease. In contrast, type 1 adjuvants like CpG-ODN, a synthetic toll-like receptor 9 agonist, inhibit the development of Th2 immunity. CpG-ODN induce type 1 and suppressive cytokines that influence Th2 cell differentiation. Here, we investigated the immune modulatory effect of CpG-ODN on allergic sensitization to OVA with alum focusing on dendritic cells (DCs) expressing the MyD88 molecule and the suppressive IL-10 cytokine. Using mice with specific cell deletion of MyD88 molecule, we showed that CpG-ODN suppressed allergic sensitization and consequent lung allergic inflammation signaling through the MyD88 pathway on dendritic cells, but not on B-cells. This inhibition was associated with an increased production of IL-10 in the bronchoalveolar lavage fluid. Sensitization to OVA with CpG-ODN of IL-10-deficient, but not wild-type mice, induced a shift towards Th1 pattern of inflammation. Employing bone marrow-derived dendritic cells (BM-DCs) pulsed with OVA for sensitizations with or without CpG-ODN, we showed that IL-10 is dispensable for the inhibition of allergic lung Th2 responses by CpG-ODN. Moreover, the lack of IL-10 on DCs was not sufficient for the CpG-ODN-induced immune-deviation towards a Th1 pattern. Accordingly, we confirmed directly the role of MyD88 pathway on DCs in the inhibition of allergic sensitization.

scholarly journals WDFY4 is required for cross-presentation in response to viral and tumor antigens

Science ◽  
2018 ◽  
Vol 362 (6415) ◽  
pp. 694-699 ◽  
Author(s):  
Derek J. Theisen ◽  
Jesse T. Davidson ◽  
Carlos G. Briseño ◽  
Marco Gargaro ◽  
Elvin J. Lauron ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Tumor Antigens ◽  
Critical Role ◽  
Tumor Rejection ◽  
Interleukin 12 ◽  
Cross Presentation ◽  
Histocompatibility Complex ◽  
Crispr Screen

During the process of cross-presentation, viral or tumor-derived antigens are presented to CD8+ T cells by Batf3-dependent CD8α+/XCR1+ classical dendritic cells (cDC1s). We designed a functional CRISPR screen for previously unknown regulators of cross-presentation, and identified the BEACH domain–containing protein WDFY4 as essential for cross-presentation of cell-associated antigens by cDC1s in mice. However, WDFY4 was not required for major histocompatibility complex class II presentation, nor for cross-presentation by monocyte-derived dendritic cells. In contrast to Batf3–/– mice, Wdfy4–/– mice displayed normal lymphoid and nonlymphoid cDC1 populations that produce interleukin-12 and protect against Toxoplasma gondii infection. However, similar to Batf3–/– mice, Wdfy4–/– mice failed to prime virus-specific CD8+ T cells in vivo or induce tumor rejection, revealing a critical role for cross-presentation in antiviral and antitumor immunity.

scholarly journals DC-Based Vaccines for Cancer Immunotherapy

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 706
Author(s):  
Chunmei Fu ◽  
Li Zhou ◽  
Qing-Sheng Mi ◽  
Aimin Jiang
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Critical Role ◽  
Cd8 T Cell ◽  
T Cell Immunity ◽  
Cell Responses ◽  
Cell Immunity

As the sentinels of the immune system, dendritic cells (DCs) play a critical role in initiating and regulating antigen-specific immune responses. Cross-priming, a process that DCs activate CD8 T cells by cross-presenting exogenous antigens onto their MHCI (Major Histocompatibility Complex class I), plays a critical role in mediating CD8 T cell immunity as well as tolerance. Current DC vaccines have remained largely unsuccessful despite their ability to potentiate both effector and memory CD8 T cell responses. There are two major hurdles for the success of DC-based vaccines: tumor-mediated immunosuppression and the functional limitation of the commonly used monocyte-derived dendritic cells (MoDCs). Due to their resistance to tumor-mediated suppression as inert vesicles, DC-derived exosomes (DCexos) have garnered much interest as cell-free therapeutic agents. However, current DCexo clinical trials have shown limited clinical benefits and failed to generate antigen-specific T cell responses. Another exciting development is the use of naturally circulating DCs instead of in vitro cultured DCs, as clinical trials with both human blood cDC2s (type 2 conventional DCs) and plasmacytoid DCs (pDCs) have shown promising results. pDC vaccines were particularly encouraging, especially in light of promising data from a recent clinical trial using a human pDC cell line, despite pDCs being considered tolerogenic and playing a suppressive role in tumors. However, how pDCs generate anti-tumor CD8 T cell immunity remains poorly understood, thus hindering their clinical advance. Using a pDC-targeted vaccine model, we have recently reported that while pDC-targeted vaccines led to strong cross-priming and durable CD8 T cell immunity, cross-presenting pDCs required cDCs to achieve cross-priming in vivo by transferring antigens to cDCs. Antigen transfer from pDCs to bystander cDCs was mediated by pDC-derived exosomes (pDCexos), which similarly required cDCs for cross-priming of antigen-specific CD8 T cells. pDCexos thus represent a new addition in our arsenal of DC-based cancer vaccines that would potentially combine the advantage of pDCs and DCexos.

scholarly journals The Role of Dendritic Cells in TB and HIV Infection

2020 ◽  
Vol 9 (8) ◽  
pp. 2661
Author(s):  
Rachel Abrahem ◽  
Emerald Chiang ◽  
Joseph Haquang ◽  
Amy Nham ◽  
Yu-Sam Ting ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Hiv Infection ◽  
Cell Response ◽  
Defense Mechanism ◽  
Critical Role ◽  
Cytokine Release ◽  
T Helper 1

Dendritic cells are the principal antigen-presenting cells (APCs) in the host defense mechanism. An altered dendritic cell response increases the risk of susceptibility of infections, such as Mycobacterium tuberculosis (M. tb), and the survival of the human immunodeficiency virus (HIV). The altered response of dendritic cells leads to decreased activity of T-helper-1 (Th1), Th2, Regulatory T cells (Tregs), and Th17 cells in tuberculosis (TB) infections due to a diminishment of cytokine release from these APCs, while HIV infection leads to DC maturation, allowing DCs to migrate to lymph nodes and the sub-mucosa where they then transfer HIV to CD4 T cells, although there is controversy around this topic. Increases in the levels of the antioxidant glutathione (GSH) plays a critical role in maintaining dendritic cell redox homeostasis, leading to an adequate immune response with sufficient cytokine release and a subsequent robust immune response. Thus, an understanding of the intricate pathways involved in the dendritic cell response are needed to prevent co-infections and co-morbidities in individuals with TB and HIV.

scholarly journals Critical Role for TNF in the Induction of Human Antigen-Specific Regulatory T Cells by Tolerogenic Dendritic Cells

2010 ◽  
Vol 185 (3) ◽  
pp. 1412-1418 ◽  
Author(s):  
Fleur S. Kleijwegt ◽  
Sandra Laban ◽  
Gaby Duinkerken ◽  
Antoinette M. Joosten ◽  
Arnaud Zaldumbide ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Regulatory T Cells ◽  
Critical Role ◽  
Tolerogenic Dendritic Cells

scholarly journals Aspergillus fumigatus Cell Wall α-(1,3)-Glucan Stimulates Regulatory T-Cell Polarization by Inducing PD-L1 Expression on Human Dendritic Cells

2017 ◽  
Vol 216 (10) ◽  
pp. 1281-1294 ◽  
Author(s):  
Emmanuel Stephen-Victor ◽  
Anupama Karnam ◽  
Thierry Fontaine ◽  
Anne Beauvais ◽  
Mrinmoy Das ◽  
...  
Keyword(s):  
Cell Wall ◽  
Dendritic Cells ◽  
T Cell ◽  
Aspergillus Fumigatus ◽  
Regulatory T Cell ◽  
Cell Polarization ◽  
T Cell Polarization ◽  
Human Dendritic Cells

scholarly journals A Critical Role of CD40 and CD70 Signaling in Conventional Type 1 Dendritic Cells in Expansion and Antitumor Efficacy of Adoptively Transferred Tumor-Specific T Cells

2020 ◽  
Vol 205 (7) ◽  
pp. 1867-1877 ◽  
Author(s):  
Takaaki Oba ◽  
Toshifumi Hoki ◽  
Takayoshi Yamauchi ◽  
Tibor Keler ◽  
Henry C. Marsh ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Critical Role ◽  
Antitumor Efficacy ◽  
Conventional Type

scholarly journals Requirement for CD8+ T cells in the development of airway hyperresponsiveness in a marine model of airway sensitization.

1996 ◽  
Vol 183 (4) ◽  
pp. 1719-1729 ◽  
Author(s):  
E Hamelmann ◽  
A Oshiba ◽  
J Paluh ◽  
K Bradley ◽  
J Loader ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Airway Hyperresponsiveness ◽  
Critical Role ◽  
Allergic Sensitization ◽  
Lung Parenchyma ◽  
Airway Responsiveness ◽  
Eosinophil Infiltration ◽  
Lymphoid Tissues

To study the role of CD8+ T cells in allergic sensitization, we examined the effects of in vivo depletion of CD8+ T cells prior to sensitization on IgE production, immediate type cutaneous hypersensitivity and development of altered airway responsiveness. BALB/c mice were thymectomized and treated with anti-CD8 antibody resulting in depletion of CD8+ T cells (<1%) in spleen and lymphoid tissues. In these mice, sensitization to ovalbumin (OVA) via the airways still resulted in IgE anti-OVA responses and immediate cutaneous reactions to OVA, but the animals were unable to develop airway hyperresponsiveness, eosinophil infiltration of the lung parenchyma, or IL-5 production in the local lymph nodes of the airway. Transfer of CD8+ T cells from naive animals during sensitization (on day 8 of the 10-d protocol) fully restored the ability to develop airway hyperresponsiveness and this was accompanied by IL-5 production and eosinophil accumulation in the lung. These data indicate a critical role for CD8+ T cells in the production of IL-5 and the development of altered airway responsiveness after antigen sensitization through the airways.

Sign in / Sign up

Export Citation Format

Share Document