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Interferon gamma interleukin 12 bcg infection

Sally A F El-Sahrigy, Azza M O Abdel Rahman, Dalia Y Samaha, Nesrine A Mohamed, Sally M Saber, Hala A Talkhan, Ghada A Ismail, Essam M Ibraheem, Emad M Riad
INTRODUCTION: Tuberculosis (TB) remains a huge worldwide burden, despite extensive vaccination coverage with the Bacillus Calmette-Guérin (BCG), the only vaccine available against this disease, indicating that BCG-driven immunity is inadequate to protect the human population against TB. This underscore the critical necessitate to develop an improved TB vaccine, based on a better understanding of host-pathogen interactions and immune responses during mycobacterial infection. AIM OF THE WORK: To examine whether the exogenous addition of IFN-β could improve dendritic cell (DC) response to Mycobacterium bovis (M...
June 2018: Journal of Immunological Methods
Ezgi Ulusoy, Neslihan Edeer Karaca, Güzide Aksu, Cengiz Çavuşoğlu, Necil Kütükçüler
AIM: Susceptibility to mycobacterial diseases is observed in some primary immunodeficiency diseases. In this study, we aimed to evaluate mycobacterial infections in primary immunodeficiency diseases. MATERIAL AND METHODS: Patients under follow-up by Ege University Pediatric Immunology Department for severe combined and combined immunodeficiencies, interleukin 12/ interferon gamma receptor deficiency, nuclear factor kappa-beta essential modulator deficiency and chronic granulomatosis disease were evaluated retrospectively in terms of the frequency and characteristics of mycobacterial infections using a questionnaire form for demographic properties, clinical features and laboratory tests...
September 2017: Türk Pediatri Arşivi
Thais Louvain de Souza, Regina C de Souza Campos Fernandes, Juliana Azevedo da Silva, Vladimir Gomes Alves Júnior, Adelia Gomes Coelho, Afonso C Souza Faria, Nabia M Moreira Salomão Simão, João T Souto Filho, Caroline Deswarte, Stéphanie Boisson-Dupuis, Dara Torgerson, Jean-Laurent Casanova, Jacinta Bustamante, Enrique Medina-Acosta
Patients with Mendelian Susceptibility to Mycobacterial Diseases (MSMD) exhibit variable vulnerability to infections by mycobacteria and other intramacrophagic bacteria (e.g., Salmonella and Klebsiella ) and fungi (e.g., Histoplasma, Candida, Paracoccidioides, Coccidioides , and Cryptococcus ). The hallmark of MSMD is the inherited impaired production of interferon gamma (IFN-γ) or the lack of response to it. Mutations in the interleukin (IL)-12 receptor subunit beta 1 ( IL12RB1 ) gene accounts for 38% of cases of MSMD...
2017: Frontiers in Microbiology
Lijiao Zhang, Yanlong Jiang, Ziyin Cui, Wentao Yang, Limin Yue, Yingcong Ma, Shaohua Shi, Chunfang Wang, Chunfeng Wang, Aidong Qian
Mycobacterium (M.) vaccae is a fast-growing species of saprophytic bacteria that is widely distributed. To understand the host immune responses induced by M. vaccae isolated from bovine submaxillary lymph nodes, C57BL/6 mice were infected with reference strain M. bovis Bacillus Calmette-Guérin (BCG) and isolated M. vaccae using intraperitoneal injections. Comparison of the bacterial replication and organ pathology between M. vaccae and M. bovis BCG revealed that M. vaccae was more malignant than M. bovis in mice...
December 30, 2016: Journal of Veterinary Science
E Bukhari, F Alaklobi, H Bakheet, A Alrabiaah, F Alotibi, F Aljobair, M Alshamrani, E Alaki, F Alnahdi, A Alodyani, F Alzamil
OBJECTIVE: The bacille Calmette Guérin (BCG) vaccine is administered worldwide to prevent tuberculosis. Although, Post BCG vaccination complications like disseminated BCG infections are rare and immunocompromised children are at high risk of developing BCG-related complications including BCG-lymphadenitis and other disseminated diseases. PATIENTS AND METHODS: This was a prospective study of children who developed disseminated BCG after vaccination who were admitted in three tertiary care hospital in Riyadh, Saudi Arabia, in the year 2015...
September 2016: European Review for Medical and Pharmacological Sciences
Lilian Martins Oliveira Diniz, Tiago Guimarães, Maria das Graças Rodrigues de Oliveira, Jorge Andrade Pinto, Silvana Spindola de Miranda
We report a rare case in a female infant (age, 3.5 months) with primary immunodeficiency (IFN-γ/IL-12 pathway defect) who presented with suppurative lymphadenitis after Mycobacterium bovis BCG vaccination. The strain of M. bovis BCG identified was found to be resistant to isoniazid and rifampin. The patient was treated with a special pharmacological regimen involving isoniazid (in a limited, strategic manner), ethambutol, streptomycin, and IFN-γ, after which there was complete resolution of the lesions.
March 2014: Jornal Brasileiro de Pneumologia: Publicaça̋o Oficial da Sociedade Brasileira de Pneumologia e Tisilogia
Kanako Takeda, Toshinao Kawai, Yumiko Nakazawa, Hisako Komuro, Kensuke Shoji, Kumiko Morita, Tomohiro Katsuta, Matsuri Yamamoto, Isao Miyairi, Yukihiro Ohya, Akira Ishiguro, Masafumi Onodera
Osteomyelitis due to Mycobacterium bovis Bacille Calmette-Guerin (BCG) often develops in patients with interferon-γ receptor 1 (IFNγR1) deficiency. In these patients, susceptibility appears to be caused by impaired interleukin-12- and IFNγ-mediated immunity. Here we report the case of a one-year-old girl with dominant partial IFNγR1 deficiency who suffered from lymphadenitis and multiple sites of osteomyelitis due to BCG infection. She was allergic to isoniazid and rifampicin--the prescribed standard treatment--and required prior desensitization therapy...
March 2014: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Y H Deng, H Y He, F J Zhang
Mycobacterium bovis bacillus Calmette-Guérin (BCG) immunization provides protection against tuberculosis (TB) in infants, but the antituberculosis protective immunity wanes gradually after initial immunization and lasts less than 15 years. Therefore, more efficacious vaccines are urgently needed. In this study, we constructed a new tuberculosis vaccine of recombinant BCG strain (rBCG-IA), which could express IL-12p70 of human cytokine and Ag85A of M. tuberculosis fusion protein, and investigated its immunogenicity in BALB/c mice by measuring antibody titres, proliferation rate of splenocytes, ratios of CD4(+) T and CD8(+) T cells stimulated by specific antigens and levels of IFN-γ production in antigen-stimulated splenocyte cultures...
December 2013: Scandinavian Journal of Immunology
Dorsaf Hedhli, Olivier Denis, Daniel Barkan, Mamadou Daffé, Michael S Glickman, Kris Huygen
The existing vaccine against tuberculosis (M. bovis BCG) exerts some protection against the extrapulmonary forms of the disease, particularly in young children, but is not very effective against the pulmonary form of TB, which often results from the reactivation of a latent M. tuberculosis (M.tb)infection. Among the new approaches in TB vaccine development, live attenuated M.tb mutants are a promising new avenue. Here we report on the vaccine potential of two highly attenuated M.tb mutants, MGM1991 and M.tbhma::hyg (HMA), lacking all oxygenated mycolates in their cell wall...
2013: PloS One
Evelina K Vetskova, Mariya N Muhtarova, Toma I Avramov, Tsvetelina R Stefanova, Ivan J Chalakov, Maria H Nikolova
BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a rare manifestation of human papilloma virus (HPV) infection with extremely high relapse frequency, poorly understood immunopathogenesis, and lack of efficient treatment. Immunotherapy with Calgevax (BCG) in combination with CO2 surgery significantly improves the outcome of RRP. The present study investigates cellular immunity parameters in RRP patients, and the effects of 20-month Calgevax immunomodulation. MATERIALS AND METHODS: RRP patients (n = 15) subjected to combined therapy were tested before, 6, 12 and 20 months after the start of immunomodulation...
January 2013: Folia Medica
Daniel W Fowler, John Copier, Angus G Dalgleish, Mark D Bodman-Smith
γδ T cells contribute to immunosurveillance of pathogenic infections and malignant transformations; however, mechanisms of activation have yet to be fully defined. In this study we demonstrate a novel mechanism by which human Vδ2(+) γδ T cells are activated by the model pathogen Bacillus Calmette Guérin (BCG). We show in vitro that Vδ2 cell cytokine production and cytotoxic activity in response to BCG are dependent on both dendritic cells (DCs) and memory CD4(+) αβ T cells (CD4 T cells). We found that Vδ2 cells are indirectly activated by BCG in an interleukin (IL)-12p70-dependent manner, and that DC production of the IL-12p70 responsible for Vδ2 cell activation requires Toll-like receptor 2/4 ligands from BCG and interferon (IFN)-γ from memory CD4 T cells...
August 2013: Immunology and Cell Biology
Jennifer D Kraft, Joseph Horzempa, Celestia Davis, Joo-Yong Jung, Maria Marjorette O Peña, Cory M Robinson
Microbial infections are a major cause of infant mortality worldwide because of impaired immune defences in this population. The nature of this work was to further understand the mechanistic limitations of the neonatal and infant immune response. Interleukin-27 (IL-27) is a heterodimeric cytokine of the IL-12 family that is produced primarily by antigen-presenting cells and is immunosuppressive toward a variety of immune cell types. We show that IL-27 gene expression is elevated in cord blood-derived macrophages relative to macrophages originating from healthy adults...
August 2013: Immunology
Gerald K Chege, Wendy A Burgers, Helen Stutz, Ann E Meyers, Rosamund Chapman, Agano Kiravu, Rubina Bunjun, Enid G Shephard, William R Jacobs, Edward P Rybicki, Anna-Lise Williamson
We previously reported that a recombinant pantothenate auxotroph of Mycobacterium bovis BCG expressing human immunodeficiency virus type 1 (HIV-1) subtype C Gag (rBCGpan-Gag) efficiently primes the mouse immune system for a boost with a recombinant modified vaccinia virus Ankara (rMVA) vaccine. In this study, we further evaluated the immunogenicity of rBCGpan-Gag in a nonhuman primate model. Two groups of chacma baboons were primed or mock primed twice with either rBCGpan-Gag or a control BCG. Both groups were boosted with HIV-1 Pr55(gag) virus-like particles (Gag VLPs)...
May 2013: Journal of Virology
Carolina Prando, Arina Samarina, Jacinta Bustamante, Stéphanie Boisson-Dupuis, Aurelie Cobat, Capucine Picard, Zobaida AlSum, Suliman Al-Jumaah, Sami Al-Hajjar, Husn Frayha, Abdullah Alangari, Hamoud Al-Mousa, Khalid F Mobaireek, Imen Ben-Mustapha, Parisa Adimi, Jacqueline Feinberg, Maylis de Suremain, Lucile Jannière, Orchidée Filipe-Santos, Nahal Mansouri, Jean-Louis Stephan, Revathy Nallusamy, Dinakantha S Kumararatne, Mohamad Reza Bloorsaz, Meriem Ben-Ali, Houda Elloumi-Zghal, Jalel Chemli, Jihene Bouguila, Mohamed Bejaoui, Emadia Alaki, Tariq S AlFawaz, Eman Al Idrissi, Gehad ElGhazali, Andrew J Pollard, Belinda Murugasu, Bee Wah Lee, Rabih Halwani, Mohammed Al-Zahrani, Mohammed A Al Shehri, Mofareh Al-Zahrani, Ibrahim Bin-Hussain, Seyed Alireza Mahdaviani, Nima Parvaneh, Laurent Abel, Davood Mansouri, Ridha Barbouche, Saleh Al-Muhsen, Jean-Laurent Casanova
Autosomal recessive interleukin (IL)-12 p40 (IL-12p40) deficiency is a rare genetic etiology of mendelian susceptibility to mycobacterial disease (MSMD). We report the genetic, immunologic, and clinical features of 49 patients from 30 kindreds originating from 5 countries (India, Iran, Pakistan, Saudi Arabia, and Tunisia). There are only 9 different mutant alleles of the IL12B gene: 2 small insertions, 3 small deletions, 2 splice site mutations, and 1 large deletion, each causing a frameshift and leading to a premature stop codon, and 1 nonsense mutation...
March 2013: Medicine (Baltimore)
Hui-feng Yang, Ze-hua Zhang, Zheng-qi Chang, Kang-lai Tang, De-zhi Lin, Jian-zhong Xu
The aim of the study is to investigate the immunological changes after stimulation with bacillus Calmette-Guerin (BCG) in mice with vitamin D deficiency. After weaning, mice were divided into the vitamin D-deficient group (-D group), the normal group (N group), and the vitamin D-supplemented group (+D group). Twelve-week-old mice were intraperitoneally injected with 0.5 mg/ml BCG (≥1.0 × 10(6) CFU/mg) and maintained for 6 weeks. Spleen lymphocytes were isolated, and the percentages of CD4(+) and CD8(+) lymphocytes were determined by flow cytometry...
November 2013: Clinical and Experimental Medicine
Wei-Jen Chua, Steven M Truscott, Christopher S Eickhoff, Azra Blazevic, Daniel F Hoft, Ted H Hansen
Mucosa-associated invariant T (MAIT) cells are a unique population of αβ T cells in mammals that reside preferentially in mucosal tissues and express an invariant Vα paired with limited Vβ T-cell receptor (TCR) chains. Furthermore, MAIT cell development is dependent upon the expression of the evolutionarily conserved major histocompatibility complex (MHC) class Ib molecule MR1. Using in vitro assays, recent studies have shown that mouse and human MAIT cells are activated by antigen-presenting cells (APCs) infected with diverse microbes, including numerous bacterial strains and yeasts, but not viral pathogens...
September 2012: Infection and Immunity
Nermeen Galal, Jeannette Boutros, Aisha Marsafy, Xiao-Fei Kong, Jacqueline Feinberg, Jean-Laurent Casanova, Stéphanie Boisson-Dupuis, Jacinta Bustamante
BACKGROUND: Tuberculosis remains a major health problem in developing countries especially with the emergence of multidrug resistant strains. Mendelian Susceptibility to Mycobacterial Disease (MSMD) is a rare disorder with impaired immunity against mycobacterial pathogens. Reported MSMD etiologies highlight the crucial role of the Interferon gamma /Interleukin 12 (IFN-γ/ IL-12) axis and the phagocyte respiratory burst axis. PURPOSE: Screen patients with possible presentations for MSMD...
2012: Mediterranean Journal of Hematology and Infectious Diseases
Rashid H Merchant, Javed Ahmed, Noor Ahmad
Mendelian Susceptibility to Mycobacterial Disease (MSMD) is a relatively new term that describes a spectrum of inherited defects in the IL-12/23 and IFN- γ pathways that result in a selective predisposition to disease caused by poorly pathogenic mycobacteria. In contrast to previous reports of patients infected with environmental mycobacteria and BCG, this manuscript elucidates the clinical course and diagnosis of MSMD in a child harboring extensively drug resistant (XDR) Mycobacterium tuberculosis.
September 2013: Indian Journal of Pediatrics
Shanmin Zhao, Yong Zhao, Fengfeng Mao, Caiqin Zhang, Bing Bai, Hai Zhang, Changhong Shi, Zhikai Xu
Tuberculosis (TB) remains a major worldwide health problem. The only vaccine against TB, Mycobacterium bovis Bacille Calmette-Guerin (BCG), has demonstrated relatively low efficacy and does not provide satisfactory protection against the disease. More efficient vaccines and improved therapies are urgently needed to decrease the worldwide spread and burden of TB, and use of a viable, metabolizing mycobacteria vaccine may be a promising strategy against the disease. Here, we constructed a recombinant Mycobacterium smegmatis (rMS) strain expressing a fusion protein of heparin-binding hemagglutinin (HBHA) and human interleukin 12 (hIL-12)...
2012: PloS One
Mary Anne Mashruwala, Amanda K Smith, Devin R Lindsey, Margaret Moczygemba, Rick A Wetsel, John R Klein, Jeffrey K Actor, Chinnaswamy Jagannath
Interferon-γ (IFNγ) plays a major role during host defense against Mycobacterium tuberculosis (Mtb). T cells produce IFNγ in response to IL-12 and IL-18 secreted from Mtb infected macrophages. IFNγ in turn, induces nitric oxide secretion in macrophages that kills Mtb. IFNγ knockout mice are thus hyper-susceptible to tuberculosis. We reported earlier that Complement-C5 deficient (C5(-/-)) congenic mice are more susceptible to tuberculosis and showed reduced IL-12 synthesis in their macrophages. Using C5(-/-) congenic mice that carry a deletion in the C5 gene and the wild type C5(+/+) mice, we demonstrate here that, the C5(-/-) derived CD3(+) T cells, have an additional defect in the synthesis of IFNγ...
December 2011: Tuberculosis
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