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

Cabral-Marques, Otávio; Arslanian, Christina; Ramos, Rodrigo Nalio; Morato, M J X; Schimke, LenaFriederike; Soeiro-Pereira, Paulo Vítor; Jancar, Sônia; Ferreira, Janaíra Fernandes Severo; Weber, Cristiane Seganfredo; Kuntze, Gisele; Rosário-Filho, Nelson Augusto; Carvalho, Beatriz; Bergami-Santos, Patrícia Cruz; Hackett, Mary J.; Ochs, Hans D.; Torgerson, Troy R.; Barbuto, José Alexandre Marzagão; Condino‐Neto, Antônio

doi:10.1016/j.jaci.2011.10.026

Cited by 31 publications

(16 citation statements)

References 35 publications

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“…In contrast, T-cell proliferation and generation of TGF-β and IL-17 were comparable with normal controls. These findings suggested that the absence of CD40L during monocyte/DC differentiation leads to functional DC abnormalities, which may contribute to the susceptibility to fungal infections in patients with CD40L deficiency (117). Four cases of T. marneffei infection were reported in CD40L deficiency (118–120).…”

Section: Pids Underlying Fungal Infectionsmentioning

confidence: 95%

Cellular and Molecular Defects Underlying Invasive Fungal Infections—Revelations from Endemic Mycoses

Lee

Lau

2017

Front. Immunol.

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The global burden of fungal diseases has been increasing, as a result of the expanding number of susceptible individuals including people living with human immunodeficiency virus (HIV), hematopoietic stem cell or organ transplant recipients, patients with malignancies or immunological conditions receiving immunosuppressive treatment, premature neonates, and the elderly. Opportunistic fungal pathogens such as Aspergillus, Candida, Cryptococcus, Rhizopus, and Pneumocystis jiroveci are distributed worldwide and constitute the majority of invasive fungal infections (IFIs). Dimorphic fungi such as Histoplasma capsulatum, Coccidioides spp., Paracoccidioides spp., Blastomyces dermatiditis, Sporothrix schenckii, Talaromyces (Penicillium) marneffei, and Emmonsia spp. are geographically restricted to their respective habitats and cause endemic mycoses. Disseminated histoplasmosis, coccidioidomycosis, and T. marneffei infection are recognized as acquired immunodeficiency syndrome (AIDS)-defining conditions, while the rest also cause high rate of morbidities and mortalities in patients with HIV infection and other immunocompromised conditions. In the past decade, a growing number of monogenic immunodeficiency disorders causing increased susceptibility to fungal infections have been discovered. In particular, defects of the IL-12/IFN-γ pathway and T-helper 17-mediated response are associated with increased susceptibility to endemic mycoses. In this review, we put together the various forms of endemic mycoses on the map and take a journey around the world to examine how cellular and molecular defects of the immune system predispose to invasive endemic fungal infections, including primary immunodeficiencies, individuals with autoantibodies against interferon-γ, and those receiving biologic response modifiers. Though rare, these conditions provide importance insights to host defense mechanisms against endemic fungi, which can only be appreciated in unique climatic and geographical regions.

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Section: Pids Underlying Fungal Infectionsmentioning

confidence: 95%

Cellular and Molecular Defects Underlying Invasive Fungal Infections—Revelations from Endemic Mycoses

Lee

Lau

2017

Front. Immunol.

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“…Both AID and UNG act downstream of CD40/CD40L in the CSR pathway and mutations in these genes lead to defects in CSR and SHM, and subsequently low serum levels of IgG, IgA, and IgE [12, 14]. Though bacterial infections are commonly seen in ARHIGM due to mutations in the AICDA/UNG genes, opportunistic pathogens are much more likely to occur in subjects with XHIGM and CD40 defects, as these defects involve impaired macrophage and T cell activation [9, 10, 15]. More complex and involving different mechanisms are the recently described autosomal dominant gain of function mutations in phosphoinositide 3-kinase catalytic delta component ( PIK3CD ) which may lead to hypogammaglobulinemia with increased serum IgM and increased susceptibility to infections, autoimmunity, lymphoid hyperplasia, and potentially lymphoma [16–19].…”

Section: Introductionmentioning

confidence: 99%

Hyper IgM Syndrome: a Report from the USIDNET Registry

et al. 2016

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Purpose The United States Immunodeficiency Network (USIDNET) patient registry was used to characterize the presentation, genetics, phenotypes, and treatment of patients with Hyper IgM Syndrome (HIGM). Methods The USIDNET Registry was queried for HIGM patient data collected from October 1992 to July 2015. Data fields included demographics, criteria for diagnosis, pedigree analysis, mutations, clinical features, treatment and transplant records, laboratory findings, and mortality. Results Fifty-two physicians entered data from 145 patients of ages 2 months to 62 years (median 12 years); 131 were males. Using patients’ age at last entry, data from 2072 patient years are included. Mutations were recorded for 85 subjects; 82 were in CD40LG. Eighteen subjects had non-X-linked HIGM. 40 % had a normal serum IgM and 15 %, normal IgA. Infections were reported for 91 %, with pulmonary, ear, and sinus infections being the most common. 42 % had Pneumocystis jirovecii pneumonia; 6 % had Cryptosporidium. 41 % had neutropenia. 78 % experienced non-infectious complications: chronic diarrhea (n = 22), aphthous ulcers (n = 28), and neoplasms (n = 8) including colon cancer, adrenal adenoma, liver adenocarcinoma, pancreatic carcinoid, acute myeloid leukemia, hepatoma, and, in a female with an autosomal dominant gain of function mutation in PIK3CD, an ovarian dysgerminoma. Thirteen patients had a hematopoietic marrow or stem cell transplant; three had solid organ transplants. Thirteen were known to have died (median age = 14 years). Conclusions Analysis of the USIDNET Registry provides data on the common clinical features of this rare syndrome, and in contrast with previously published data, demonstrates longer survival times and reduced gastrointestinal manifestations.

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“…This is accompanied by reduced IL-12 and elevated IL-10 release and impaired induction of T-cell activation and proliferation. Curiously, very similar effects on DC function are found in patients with CD40L deficiency, where monocytederived DC also demonstrate lower expression of MHCII and co-stimulatory molecules and imbalanced IL-12/IL-10 release that can be rescued by co-culture with soluble CD40L but not with other physiological stimuli (Cabral-Marques et al 2012). DC from patients with CD40L deficiency are capable of inducing normal autologous T-cell proliferation, but with perturbed Tcell cytokine production towards a T H 2 phenotype.…”

Section: Hyper Igm Syndromesmentioning

confidence: 81%

Dendritic cell defects in primary immunodeficiency disorders

Burns

2016

LymphoSign Journal

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Dendritic cells (DC) are professional antigen-presenting cells that play a key role in linking the innate and adaptive arms of the immune system. In vitro, DC perform critical functions such as antigen uptake and processing, priming of naïve T cells and production of cytokines to regulate other immune cells. In vivo experimental systems support a central role for DC in inducing protective immune responses but the effect of DC deficiency in existing whole animal models is smaller than would be predicted. Studies of human primary immunodeficiency disorders (PID) have significantly advanced our understanding of the development and function of other immune cells and provide some important information about DC. Although only a small number of rare monogenic PID that cause DC deficiency have been described to date, impaired DC function forms part of the immunophenotype of several PID and is likely to contribute to clinical presentation. This review focuses on what is known so far about the role of DC in PID and what implications this has for basic DC biology.

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

Cited by 31 publications

References 35 publications

Cellular and Molecular Defects Underlying Invasive Fungal Infections—Revelations from Endemic Mycoses

Cellular and Molecular Defects Underlying Invasive Fungal Infections—Revelations from Endemic Mycoses

Hyper IgM Syndrome: a Report from the USIDNET Registry

Dendritic cell defects in primary immunodeficiency disorders

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