Abnormal Regulation of Interferon‐γ, Interleukin‐12, and Tumor Necrosis Factor‐α in Human Interferon‐g Receptor 1 Deficiency

Holland, Steven M.; Dorman, Susan E.; Kwon, Annette; Pitha-Rowe, Ian; Frucht, David M.; Gerstberger, Susan; Noel, Gary J.; Vesterhus, Per; Brown, Margaret R.; Fleisher, Thomas A.

doi:10.1086/515670

Cited by 146 publications

(90 citation statements)

References 4 publications

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“…They started to examine candidate genes and found that mutations in the IFNgR1 gene could lead to disseminated BCG infection at the same time as Levin's group found they caused recurrent atypical mycobacterial infections. 80 The IFNgR1 gene mutations are inherited as autosomal recessive traits and either abolish receptor expression 78,[80][81][82][83][84][85] or binding of the receptor to IFNg. [86][87] Partial IFNgR1 deficiency has also been described in two siblings, one of whom developed disseminated BCG infection and the other clinical tuberculosis.…”

Section: Familial Atypical Mycobacteriosis and Abnormal Ifng Signallingmentioning

confidence: 99%

Susceptibility to mycobacterial infections: the importance of host genetics

2003

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There is substantial evidence that host genetic factors are important in determining susceptibility to mycobacteria. Several different techniques have been used to identify the genes involved. Studies of an inbred strain of mice with increased susceptibility to mycobacteria, salmonella and leishmania infections led to the identification of the natural resistance-associated macrophage protein gene (Nramp1). Case-control studies have confirmed the importance of the human equivalent of this gene, NRAMP1, and have also suggested that the major histocompatibility complex and vitamin-D receptor genes may be involved in determining human susceptibility to mycobacteria. Studies of individuals with the rare condition of increased susceptibility to disseminated bacille Calmette-Guerin and other atypical mycobacterial infections have identified several abnormalities in the genes encoding the interferon gamma receptor (IFNgR) ligand binding chain, IFNgR signal transduction chain, IFNg signal transduction and activation of transcription-1, interleukin 12 receptor b1 subunit and interleukin 12 p40 subunit. A genome-wide linkage study has been performed to identify genes exerting a major effect on tuberculosis susceptibility in the general population. Linkages were found to markers on chromosomes 15 and X. Studies to identify the genes responsible are in progress.

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Section: Familial Atypical Mycobacteriosis and Abnormal Ifng Signallingmentioning

confidence: 99%

Susceptibility to mycobacterial infections: the importance of host genetics

2003

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“…Mutations in five different genes produce this disorder: IFN-GR1, IFN-GR2, STAT1, IL12B, and IL12RB1. The main clinical characteristic of these patients is their higher susceptibility to the development of disseminated mycobacterial disease or local recurrent infections by non-tuberculosis mycobacteria and, in some cases, chronic infections by other agents such as Salmonella species and certain viruses (20,(22)(23)(24)(25)(26)(27)(29)(30)(31)(32)(33)(34)(35)(36). Many of these characteristics are similar to the clinical features observed in our patients (Table 3); therefore, a defect in one of the molecules involved in the IL-12/IFN-γ/IFN-γR/STAT-1 activation pathway is a possible explanation for their phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…These patients exhibit systemic infections and inability to develop mature granulomas in response to mycobacteria and frequently die as a consequence of this infection. Microorganisms other than mycobacteria such as Salmonella and some viruses also produce severe infections (20)(21)(22)(23)(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Normal expression of IFN-gammaR in four patients with uncommon mycobacterial infection phenotypes

Rugeles

Rincón

Rugeles

et al. 2004

Braz J Med Biol Res

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Several primary immunodeficiency diseases affecting the interleukin 12/interferon gamma (IFN-γ) pathway have been identified, most of them characterized by recurrent and protracted infections produced by intracellular microorganisms, particularly by several species of mycobacteria. In the present study we analyzed the expression of IFN-γ receptor (IFN-γR) and signal transducer and activator of transcription 1 (STAT-1) in 4 children with Mycobacterium tuberculosis infection of uncommon clinical presentation. These molecules were evaluated by flow cytometry and Western blotting in B cells transformed with Epstein-Barr virus and mutations were scanned by single-strand conformational polymorphisms and DNA sequencing. The expression of IFN-γR1 was normal in all 4 patients. The genetic analysis of IFN-γR1 and IFN-γR2 coding sequences did not reveal any mutation. The expression of the STAT-1 molecule was similar in patients and healthy controls; however, when the phosphorylation of this transcription factor in response to IFN-γ activation was evaluated by Western blot, a significant lower signal was evident in one patient. These data indicate that there are no alterations in the expression or function of the IFN-γR chains in these patients. However, the low level of STAT-1 phosphorylation found in one of these patients might be explained by a defect in one of the molecules involved in the signal transduction pathway after IFN-γ interacts with its receptor. In the other three patients the inability to eliminate the mycobacteria may be due to a defect in another effector mechanism of the mononuclear phagocytes.

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“…Among all these cells, CD4 and CD8 T cells are important in producing INF-γ, one of the main cytokines involved in the immune response. Its importance has been shown in some studies [7][8][9][10] where INF-γ gene knockout or the lack of its receptor led to higher susceptibility to Mycobacterium tuberculosis.…”

Section: Importance Of Cellular Immunity In Tuberculosismentioning

confidence: 99%

Macrophage Infection by Mycobacteria

Saleh¹

2016

Mycobact Dis

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Mycobacterium tuberculosis is the etiological agent of tuberculosis. It is a pathogen that continues to draw international concerns particularly due to the emergence of multi-drug resistance and to the difficulties associated with the diagnosis and treatment of latent tuberculosis. A key process in the pathogenesis of this disease is the interaction between this pathogen and host macrophages. Invasion of the macrophages protects the pathogen from attack by the immune system, allows it to multiply while protected within the macrophages, and alters the immune response as it influences the profiles of the cytokine and chemokine responses. Key to the intracellular survival of the pathogen within the macrophages is the specific interaction between the pathogen and its virulence factors with the host. This review provides an a summary of pertinent literature on the topic of macrophage receptors utilized by the pathogen, its survival strategies within the macrophage, and the general profile of immune signalling upon exposure to the pathogen. The importance of specific macrophage receptors and certain components of the pathogen to the direction of the immune response are also discussed.

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Abnormal Regulation of Interferon‐γ, Interleukin‐12, and Tumor Necrosis Factor‐α in Human Interferon‐g Receptor 1 Deficiency

Cited by 146 publications

References 4 publications

Susceptibility to mycobacterial infections: the importance of host genetics

Susceptibility to mycobacterial infections: the importance of host genetics

Normal expression of IFN-gammaR in four patients with uncommon mycobacterial infection phenotypes

Macrophage Infection by Mycobacteria

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