Paracoccidioides brasiliensis Disseminated Disease in a Patient with Inherited Deficiency in the  1 Subunit of the Interleukin (IL)-12/IL-23 Receptor

Moraes-Vasconcelos, Dewton; Grumach, Anete Sevciovic; Yamaguti, Augusto; Andrade, Maria Elisa Bertocco; Fieschi, Claire; Beaucoudrey, Ludovic de; Casanova, Jean‐Laurent; Duarte, Alberto J. S.

doi:10.1086/432119

Cited by 103 publications

(63 citation statements)

References 38 publications

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“…These combined immunological defects leave IL12RB1 mut individuals more susceptible to infection by mycobacteria, Salmonella, and Candida species, as reported in a recent extensive international study (20). Smaller and more regional studies have also shown positive associations between IL12RB1 deficiencies (13,14,21,23,(51)(52)(53) or IL12RB1 polymorphisms (16,22,(54)(55)(56)(57) and susceptibility to a number of other maladies and infectious diseases. However, notably, beneficial IL12RB1 polymorphisms also have been discovered (58,59).…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Signals Direct Expression of Human IL12RB1 into Multiple Distinct Isoforms

Ford

Miller

Reeme

et al. 2012

The Journal of Immunology

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IL12RB1 is essential for human resistance to multiple intracellular pathogens, including Mycobacterium tuberculosis. In its absence, the proinflammatory effects of the extracellular cytokines IL-12 and IL-23 fail to occur, and intracellular bacterial growth goes unchecked. Given the recent observation that mouse leukocytes express more than one isoform from il12rb1, we examined whether primary human leukocytes similarly express more than one isoform from IL12RB1. We observed that human leukocytes express as many as 13 distinct isoforms, the relative levels of each being driven by inflammatory stimuli both in vitro and in vivo. Surprisingly, the most abundant isoform present before stimulation is a heretofore uncharacterized intracellular form of the IL-12R (termed “isoform 2”) that presumably has limited contact with extracellular cytokine. After stimulation, primary PBMCs, including the CD4+, CD8+, and CD56+ lineages contained therein, alter the splicing of IL12RB1 RNA to increase the relative abundance of isoform 1, which confers IL-12/IL-23 responsiveness. These data demonstrate both a posttranscriptional mechanism by which cells regulate their IL-12/IL-23 responsiveness, and that leukocytes primarily express IL12RB1 in an intracellular form located away from extracellular cytokine.

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Section: Discussionmentioning

confidence: 99%

Inflammatory Signals Direct Expression of Human IL12RB1 into Multiple Distinct Isoforms

Ford

Miller

Reeme

et al. 2012

The Journal of Immunology

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“…Deficient production of certain cytokines, such as IFN-γ, IL-12, and IL-23, as well as of their receptors, predisposes patients to TB and to PCM. (5) The pattern of cytokine production by CD4 + T lymphocytes can determine the severity of the clinical profile of these two diseases. The predominance of IFN-γ (produced by CD4 + T lymphocytes known as T helper 1 cells) is generally associated with a more favorable clinical evolution, whereas the predominance of IL-4, IL-5, and IL-10 (produced by CD4 + T lymphocytes designated T helper 2 cells) results in a more severe disease progression.…”

Section: Discussionmentioning

confidence: 99%

“…(3,4) Deficient production of certain cytokines, such as interleukin (IL)-12, IL-23, and interferon gamma (IFN-γ), as well as of their receptors, predisposes patients to TB and to PCM. (5) Since the clinical presentation of these diseases can be similar, it has been observed that several patients definitively diagnosed with PCM had been previously treated for TB, although without sputum smear microscopy confirmation. Most of those patients did not respond to specific anti-TB treatment and only improved after drug treatment for PCM had been started.…”

Section: Introductionmentioning

confidence: 99%

Associação entre paracoccidioidomicose e tuberculose: realidade e erro diagnóstico

et al. 2007

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Objective: To evaluate the frequency of the real association between paracoccidioidomycosis (PCM) and tuberculosis (TB) as well as the rate of previous TB misdiagnosis in individuals with PCM among the patients treated in the Pulmonology Division of the State University of Campinas Hospital das Clínicas, Campinas, Brazil. Methods: A retrospective study of 227 adult patients with PCM (chronic form) treated between 1980 and 2005. Results: Of the 227 patients studied, 36 (15.8%) had been previously treated for TB. However, only 18 (7.9%) presented positive sputum smear microscopy results. The remaining 18 (7.9%) neither presented positive sputum smear microscopy nor showed improvement after receiving specific anti-TB treatment. Conclusion: Although the existence of an association between PCM and TB has been documented in the literature, misdiagnosis is common due to the superimposition of and the similarity between their clinical and radiographic presentations, thereby warranting the need for bacteriological diagnosis before initiating specific treatment.

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“…The defect is a result of an interstitial deletion that creates a signal-impaired but cell-surfacepersisting molecule that exerts a dominant-negative effect on IFN-g cellular responses of the wild-type receptor. Furthermore, coccidioidomycosis, histoplasmosis, paracoccidioidomycosis and cryptococcosis have been reported in patients with missense homozygous or heterozygous mutations in the b1 subunit of IL-12R (Moraes-Vasconcelos et al 2005;Rezai et al 2008;de Beaucoudrey et al 2010;Vinh et al 2011). Although cellular responses to IFN-g are unaffected in these patients, IL-12-dependent IFN-g production is impaired.…”

Section: Disorders In Cytokine Signaling Il-12/ifn-g Signalingmentioning

confidence: 99%

Mendelian Genetics of Human Susceptibility to Fungal Infection

Lionakis

Netea

Holland

2014

Cold Spring Harbor Perspectives in Medicine

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Correspondence: lionakism@niaid.nih.gov A recent surge in newly described inborn errors of immune function-related genes that result in susceptibility to fungal disease has greatly enhanced our understanding of the cellular and molecular basis of antifungal immune responses. Characterization of single-gene defects that predispose to various combinations of superficial and deep-seated infections caused by yeasts, molds, and dimorphic fungi has unmasked the critical role of novel molecules and signaling pathways in mucosal and systemic antifungal host defense. These experiments of nature offer a unique opportunity for developing new knowledge in immunological research and form the foundation for devising immune-based therapeutic approaches for patients infected with fungal pathogens.

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Paracoccidioides brasiliensis Disseminated Disease in a Patient with Inherited Deficiency in the 1 Subunit of the Interleukin (IL)-12/IL-23 Receptor

Cited by 103 publications

References 38 publications

Inflammatory Signals Direct Expression of Human IL12RB1 into Multiple Distinct Isoforms

Inflammatory Signals Direct Expression of Human IL12RB1 into Multiple Distinct Isoforms

Associação entre paracoccidioidomicose e tuberculose: realidade e erro diagnóstico

Mendelian Genetics of Human Susceptibility to Fungal Infection

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