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Interferon gamma interleukin 12 bcg infection

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
Bo-Young Jeon, Hyungjin Eoh, Sang-Jun Ha, Hyeeun Bang, Seung-Cheol Kim, Young-Chul Sung, Sang-Nae Cho
PURPOSE: Bacillus Calmette-Guérin (BCG) vaccine has widely been used to immunize against tuberculosis, but its protective efficacy is variable in adult pulmonary tuberculosis, while it is not efficiently protective against progressive infection of virulent Mycobacterium tuberculosis strains. In this study, the protective effects of plasmid DNA vaccine constructs encoding IL-12 or IL-18 with the BCG vaccine were evaluated against progressive infection of M. tuberculosis, using mouse aerosol challenge model...
November 2011: Yonsei Medical Journal
Léanie Kleynhans, Nelita Du Plessis, Gillian F Black, André G Loxton, Martin Kidd, Paul D van Helden, Gerhard Walzl, Katharina Ronacher
Most individuals latently infected with Mycobacterium tuberculosis (M.tb) contain the infection by a balance of effector and regulatory immune responses. This balance can be influenced by steroid hormones such as glucocorticoids. The widely used contraceptive medroxyprogesterone acetate (MPA) possesses glucocorticoid activity. We investigated the effect of this hormone on immune responses to BCG in household contacts of active TB patients. Multiplex bead array analysis revealed that MPA demonstrated both glucocorticoid and progestogenic properties at saturating and pharmacological concentrations in peripheral blood mononuclear cells (PBMCs) and suppressed antigen specific cytokine production...
2011: PloS One
Rabia Hussain, Najeeha Talat, Ambreen Ansari, Firdaus Shahid, Zahra Hasan, Ghaffar Dawood
OBJECTIVE: Dynamic cytokine profiles from endogenously activated T cells in transit from lymph node to the infected sites via the blood compartment after recent exposure to Mycobacterium tuberculosis may differentiate disease progressors from non-disease progressors in a BCG-vaccinated population. METHODS: Household contacts (N = 107) from families with (six families) or without (14 families) secondary cases were assessed for Types 1 and 2 cytokines serially in plasma of whole blood cultures without exogenous stimulation...
October 2011: Journal of Clinical Immunology
Masaji Okada, Yoko Kita, Toshihiro Nakajima, Noriko Kanamaru, Satomi Hashimoto, Tetsuji Nagasawa, Yasufumi Kaneda, Shigeto Yoshida, Yasuko Nishida, Hitoshi Nakatani, Kyoko Takao, Chie Kishigami, Shiho Nishimatsu, Yuki Sekine, Yoshikazu Inoue, David N McMurray, Mitsunori Sakatani
OBJECTIVE: Mycobacterium tuberculosis infection is a major global threat to human health. The only tuberculosis (TB) vaccine currently available is bacillus Calmette-Guérin (BCG), although it has no efficacy in adults. Therefore, the development of a novel vaccine against TB for adults is desired. METHOD: A novel TB vaccine expressing mycobacterial heat shock protein 65 (HSP65) and interleukin-12 (IL-12) delivered by the hemagglutinating virus of Japan- (HVJ)- envelope was evaluated against TB infection in mice...
2011: Clinical & Developmental Immunology
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