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Tuberculosis immunity

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https://www.readbyqxmd.com/read/29330469/mycobacterium-tuberculosis-exploits-a-molecular-off-switch-of-the-immune-system-for-intracellular-survival
#1
Ulrich von Both, Maurice Berk, Paul-Michael Agapow, Joseph D Wright, Anna Git, Melissa Shea Hamilton, Greg Goldgof, Nazneen Siddiqui, Evangelos Bellos, Victoria J Wright, Lachlan J Coin, Sandra M Newton, Michael Levin
Mycobacterium tuberculosis (M. tuberculosis) survives and multiplies inside human macrophages by subversion of immune mechanisms. Although these immune evasion strategies are well characterised functionally, the underlying molecular mechanisms are poorly understood. Here we show that during infection of human whole blood with M. tuberculosis, host gene transcriptional suppression, rather than activation, is the predominant response. Spatial, temporal and functional characterisation of repressed genes revealed their involvement in pathogen sensing and phagocytosis, degradation within the phagolysosome and antigen processing and presentation...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29328912/bcg-educates-hematopoietic-stem-cells-to-generate-protective-innate-immunity-against-tuberculosis
#2
Eva Kaufmann, Joaquin Sanz, Jonathan L Dunn, Nargis Khan, Laura E Mendonça, Alain Pacis, Fanny Tzelepis, Erwan Pernet, Anne Dumaine, Jean-Christophe Grenier, Florence Mailhot-Léonard, Eisha Ahmed, Jad Belle, Rickvinder Besla, Bruce Mazer, Irah L King, Anastasia Nijnik, Clinton S Robbins, Luis B Barreiro, Maziar Divangahi
The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune training. However, the underlying mechanisms and location for generating such innate memory responses in vivo remain unknown. Here, we show that access of Bacillus Calmette-Guérin (BCG) to the bone marrow (BM) changes the transcriptional landscape of hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), leading to local cell expansion and enhanced myelopoiesis at the expense of lymphopoiesis...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29326867/cavitary-lung-lesion-suspicious-for-malignancy-reveals-mycobacterium-xenopi
#3
Sumit Fogla, Vaishali M Pansare, Luis G Camero, Uzma Syeda, Naveen Patil, Arun Chaudhury
We report the case of a 68-year-old gentleman who presented with musculoskeletal chest pain which appeared suddenly when he bent over with his dog. The chest pain was localized to the left lower chest and increased with movement and deep breathing. The patient did not complain weight loss, night sweat, fever or chill. He complained of mild cough, with expectoration of whitish mucus. Imaging revealed cavitary chest lesion in the right upper lobe, which was initially suspected to be lung cancer. The patient had a 50-year-old history of smoking 2 packs per day...
2018: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/29324800/hepcidin-deficiency-and-iron-deficiency-do-not-alter-tuberculosis-susceptibility-in-a-murine-m-tb-infection-model
#4
Rachel Harrington-Kandt, Elena Stylianou, Lucy A Eddowes, Pei Jin Lim, Lisa Stockdale, Nawamin Pinpathomrat, Naomi Bull, Janet Pasricha, Marta Ulaszewska, Yulia Beglov, Sophie Vaulont, Hal Drakesmith, Helen McShane
Tuberculosis (TB), caused by the macrophage-tropic pathogen Mycobacterium tuberculosis (M.tb) is a highly prevalent infectious disease. Since an immune correlate of protection or effective vaccine have yet to be found, continued research into host-pathogen interactions is important. Previous literature reports links between host iron status and disease outcome for many infections, including TB. For some extracellular bacteria, the iron regulatory hormone hepcidin is essential for protection against infection...
2018: PloS One
https://www.readbyqxmd.com/read/29324233/bcg-vaccination-protects-against-experimental-viral-infection-in-humans-through-the-induction-of-cytokines-associated-with-trained-immunity
#5
Rob J W Arts, Simone J C F M Moorlag, Boris Novakovic, Yang Li, Shuang-Yin Wang, Marije Oosting, Vinod Kumar, Ramnik J Xavier, Cisca Wijmenga, Leo A B Joosten, Chantal B E M Reusken, Christine S Benn, Peter Aaby, Marion P Koopmans, Hendrik G Stunnenberg, Reinout van Crevel, Mihai G Netea
The tuberculosis vaccine bacillus Calmette-Guérin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide epigenetic reprograming of monocytes and protected against experimental infection with an attenuated yellow fever virus vaccine strain. Epigenetic reprogramming was accompanied by functional changes indicative of trained immunity...
January 10, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29322681/gut-microbiome-contributes-to-impairment-of-immunity-in-pulmonary-tuberculosis-patients-by-alteration-of-butyrate-and-propionate-producers
#6
Abhijit Maji, Richa Misra, Darshan B Dhakan, Vipin Gupta, Nitish K Mahato, Rituja Saxena, Parul Mittal, Nitin Thukral, Eshan Sharma, Anoop Singh, Richa Virmani, Mohita Gaur, Harshvardhan Singh, Yasha Hasija, Gunjan Arora, Anurag Agrawal, Anil Chaudhry, Jitendra P Khurana, Vineet K Sharma, Rup Lal, Yogendra Singh
Tuberculosis (TB) is primarily associated with decline in immune health status. As gut microbiome (GM) is implicated in the regulation of host immunity and metabolism, here we investigate GM alteration in TB patients by 16S rRNA gene and whole-genome shotgun sequencing. The study group constituted of patients with pulmonary TB and their healthy household contacts as controls (HCs). Significant alteration of microbial taxonomic and functional capacity was observed in patients with active TB as compared to the HCs...
January 2018: Environmental Microbiology
https://www.readbyqxmd.com/read/29321691/deciphering-the-nature-of-the-coral-chromera-association
#7
Amin R Mohamed, Vivian R Cumbo, Saki Harii, Chuya Shinzato, Cheong Xin Chan, Mark A Ragan, Nori Satoh, Eldon E Ball, David J Miller
Since the discovery of Chromera velia as a novel coral-associated microalga, this organism has attracted interest because of its unique evolutionary position between the photosynthetic dinoflagellates and the parasitic apicomplexans. The nature of the relationship between Chromera and its coral host is controversial. Is it a mutualism, from which both participants benefit, a parasitic relationship, or a chance association? To better understand the interaction, larvae of the common Indo-Pacific reef-building coral Acropora digitifera were experimentally infected with Chromera, and the impact on the host transcriptome was assessed at 4, 12, and 48 h post-infection using Illumina RNA-Seq technology...
January 10, 2018: ISME Journal
https://www.readbyqxmd.com/read/29320502/impaired-ifn-%C3%AE-mediated-signal-in-dendritic-cells-differentiates-active-from-latent-tuberculosis
#8
Stefania Parlato, Teresa Chiacchio, Debora Salerno, Linda Petrone, Luciano Castiello, Giulia Romagnoli, Irene Canini, Delia Goletti, Lucia Gabriele
Individuals exposed to Mycobacterium tuberculosis (Mtb) may be infected and remain for the entire life in this condition defined as latent tuberculosis infection (LTBI) or develop active tuberculosis (TB). Among the multiple factors governing the outcome of the infection, dendritic cells (DCs) play a major role in dictating antibacterial immunity. However, current knowledge on the role of the diverse components of human DCs in shaping specific T-cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets as well as of monocyte-derived Interferon-α DCs (IFN-DCs) from patients with active TB, subjects with LTBI and healthy donors (HD)...
2018: PloS One
https://www.readbyqxmd.com/read/29317823/european-perspective-on-the-management-of-rheumatoid-arthritis-clinical-utility-of-tofacitinib
#9
REVIEW
Paweł Kawalec, Katarzyna Śladowska, Iwona Malinowska-Lipień, Tomasz Brzostek, Maria Kózka
Xeljanz® (tofacitinib) is an oral small-molecule inhibitor that reversibly inhibits Janus-activated kinase (JAK)-dependent cytokine signaling, thus reducing inflammation. As a result of these mechanisms, effects on the immune system such as a moderate decrease in the total lymphocyte count, a dose-dependent decrease in natural killer (NK) cell count, and an increase in B-cell count have been observed. Therefore, tofacitinib provides an innovative approach to modulating the immune and inflammatory responses in patients with rheumatoid arthritis (RA), which is especially important in individuals who do not respond to tumor necrosis factor inhibitors or show a loss of response over time...
2018: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29316546/tuberculosis-associated-chylothorax-case-report-and-systematic-review-of-the-literature
#10
Srinivas Rajagopala, Roopa Kancherla, Ramanathan Palaniappan Ramanathan
Tuberculosis (TB) is a rare cause of chylothorax. We describe a case and the results of a systematic review of all reported cases of TB-chylothorax. We identified 37 cases of TB-chylothorax. The symptoms at presentation were constitutional (85.7%; 30/35), dyspnea (60.6%; 20/33), and cough (54.5%; 18/33). Chylothorax developed subsequent to the diagnosis of TB in 27.8% (10/36) of the patients, after a median of 6.75 weeks (IQR 4-9). Chylothorax developed during an immune reconstitution syndrome (IRS) in 16.7% (10/36) of the patients, including immunocompetent ones...
January 9, 2018: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/29316047/parainfluenza-virus-5-vectored-vaccines-against-human-and-animal-infectious-diseases
#11
REVIEW
Zhenhai Chen
Parainfluenza virus 5 (PIV5), known as canine parainfluenza virus in the veterinary field, is a negative-sense, nonsegmented, single-stranded RNA virus belonging to the Paramyxoviridae family. Parainfluenza virus 5 is an excellent viral vector and has been used as a live vaccine for kennel cough for many years in dogs without any safety concern. It can grow to high titers in many cell types, and its genome is stable even in the presence of foreign gene insertions. So far, PIV5 has been used to develop vaccines against influenza virus, respiratory syncytial virus, rabies virus, and Mycobacterium tuberculosis, demonstrating its ability to elicit robust and protective immune responses in preclinical animal models...
January 5, 2018: Reviews in Medical Virology
https://www.readbyqxmd.com/read/29313424/why-macrophages-cannot-lap-up-tb
#12
Stefan Köster, Sandeep Upadhyay, Jennifer A Philips
M. tuberculosis causes an enormous worldwide burden of disease. Its success depends upon subverting the antimicrobial capacity of macrophages. We have known for decades that M. tuberculosis impairs phagosomal trafficking to avoid lysosomal degradation, but the mechanism is unclear. Recent work has described a phagolysosomal pathway called LC3-associated phagocytosis (LAP), in which LC3 associates with microbe-containing phagosomes. Macrophage pathogen recognition receptors (PRRs) initiate LAP, and NADPH oxidase and RUBCN/RUBICON are required for LAP...
January 9, 2018: Autophagy
https://www.readbyqxmd.com/read/29311492/innate-immunity-mediated-by-dendritic-cells-macrophages-plays-a-central-role-in-the-early-period-in-tumor-treatment-using-gene-of-mycobacterium-tuberculosis-antigen
#13
Takahiro Ushigusa, Yoshiyuki Koyama, Tomoko Ito, Kenichi Watanabe, James K Chambers, Aya Hasegawa, Kazuyuki Uchida, Ryoji Kanegi, Shingo Hatoya, Toshio Inaba, Kikuya Sugiura
By using a complex of DNA, polyethylenimine and chondroitin sulfate, the in vivo transfection of early secretory antigenic target-6 (ESAT-6) gene into tumor cells was found to cause significant suppression of the tumor growth. In order to apply the method in clinical cancer treatment in dogs and cats, mechanisms underlying the suppressive effects were investigated in a tumor-bearing mouse model. The transfection efficiency was only about 10%, but the transfection of ESAT-6 DNA nevertheless induced systemic immune responses against ESAT-6...
January 1, 2018: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/29310595/potential-of-dosr-and-rpf-antigens-from-mycobacterium-tuberculosis-to-discriminate-between-latent-and-active-tuberculosis-in-a-tuberculosis-endemic-population-of-medellin-colombia
#14
Leonar Arroyo, Diana Marín, Kees L M C Franken, Tom H M Ottenhoff, Luis F Barrera
BACKGROUND: Tuberculosis (TB) remains one of the most deadly infectious diseases. One-third to one-fourth of the human population is estimated to be infected with Mycobacterium tuberculosis (Mtb) without showing clinical symptoms, a condition called latent TB infection (LTBI). Diagnosis of Mtb infection is based on the immune response to a mixture of mycobacterial antigens (PPD) or to Mtb specific ESAT-6/CFP10 antigens (IGRA), highly expressed during the initial phase of infection. However, the immune response to PPD and IGRA antigens has a low power to discriminate between LTBI and PTB...
January 8, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29300789/mycobacterium-tuberculosis-induced-mir-155-subverts-autophagy-by-targeting-atg3-in-human-dendritic-cells
#15
Marilena P Etna, Alessandro Sinigaglia, Angela Grassi, Elena Giacomini, Alessandra Romagnoli, Manuela Pardini, Martina Severa, Melania Cruciani, Fabiana Rizzo, Eleni Ananstasiadou, Barbara Di Camillo, Luisa Barzon, Gian Maria Fimia, Riccardo Manganelli, Eliana M Coccia
Autophagy is a primordial eukaryotic pathway, which provides the immune system with multiple mechanisms for the elimination of invading pathogens including Mycobacterium tuberculosis (Mtb). As a consequence, Mtb has evolved different strategies to hijack the autophagy process. Given the crucial role of human primary dendritic cells (DC) in host immunity control, we characterized Mtb-DC interplay by studying the contribution of cellular microRNAs (miRNAs) in the post-transcriptional regulation of autophagy related genes...
January 4, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29295582/theoretical-and-experimental-comparison-of-different-formats-of-immunochromatographic-serodiagnostics
#16
Dmitriy V Sotnikov, Anatoly V Zherdev, Boris B Dzantiev
In this study, a comparative theoretical and experimental analysis of two immuno-chromatographic serodiagnostics schemes, which differ in the immobilization of immunoreagents and the order of the formation of immune complexes, is performed. Based on the theoretical models, the assays are characterized to determine which scheme has a higher quantity of the detected complex and thus ensures the sensitivity of the analysis. The results show that for the effective detection of low-affinity antibodies, the scheme involving the immobilization of the antigen on gold nanoparticles and the antibody-binding protein on the test strip was more sensitive than the predominantly used scheme, which inverts the immunoreagents' locations...
December 25, 2017: Sensors
https://www.readbyqxmd.com/read/29291452/ifn-%C3%AE-decreased-the-suppressive-function-of-cd33-hla-drlow-myeloid-cells-through-down-regulation-of-pd-1-pd-l2-signaling-pathway
#17
Xiaoxia Zhan, Shengfeng Hu, Yongjian Wu, Miao Li, Ting Liu, Siqi Ming, Minhao Wu, Min Liu, Xi Huang
Myeloid-derived suppressor cells (MDSCs) have recently been described to inhibit protective T-cell responses in tuberculosis (TB). T cells play an important role in the immunity to Mycobacterium tuberculosis, and are the major producers of IFN-γ. However, the impact of IFN-γ on MDSCs during TB is still not completely understood. Our study demonstrated a significant correlation between MDSC levels and TB progression, suggesting that MDSCs may serve as a potential marker in diagnosis or treatment of TB. Culture with GM-csf and IL-6 promoted peripheral blood mononuclear cells (PBMCs) to differentiate into functional CD33+HLA-DRlow MDSC-like cells...
December 29, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29281987/orfeome-based-identification-of-biomarkers-for-serodiagnosis-of-mycobacterium-tuberculosis-latent-infection
#18
Fangbin Zhou, Xindong Xu, Sijia Wu, Xiaobing Cui, Weiqing Pan
BACKGROUND: The challenges posed by Mycobacterium tuberculosis infection require the gradual removal of the pool of latent tuberculosis infection (LTBI). The current cell-immune-based diagnostic tests used to identify LTBI individuals have several irreversible drawbacks. In the present study, we attempted to identify novel diagnostic antigens for LTBI. METHODS: A high-throughput glutathione S-transferase (GST)-fusion technology was used to express over 409 TB proteins and sera from LTBI and healthy individuals was used to interrogate these GST-TB fusion proteins...
December 28, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29279479/fatal-disseminated-tuberculosis-during-treatment-with-ruxolitinib-plus-prednisolone-in-a-patient-with-primary-myelofibrosis-a-case-report-and-review-of-the-literature
#19
Yasuhiro Tsukamoto, Junichi Kiyasu, Mariko Tsuda, Motohiko Ikeda, Motoaki Shiratsuchi, Yoshihiro Ogawa, Yuji Yufu
A 73-year-old man with primary myelofibrosis (PMF) was being treated with hydroxyurea, which was changed to ruxolitinib treatment because of worsening constitutional symptoms. Although ruxolitinib rapidly induced relief, he developed a high-grade fever. A comprehensive fever work-up found no apparent cause of the fever, except for PMF. Therefore, we increased the dose of ruxolitinib and added prednisolone, which was gradually withdrawn with resolution of the fever. However, the patient subsequently developed disseminated tuberculosis and died eight months after initiation of ruxolitinib...
December 27, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29273131/association-between-atopic-dermatitis-and-serious-cutaneous-multiorgan-and-systemic-infections-in-us-adults
#20
Shanthi Narla, Jonathan I Silverberg
BACKGROUND: Atopic dermatitis (AD) is associated with barrier disruption, immune dysregulation, and immunosuppressing treatments that can increase the association with an unusual number of infections. OBJECTIVE: To determine whether adults with AD have an unusually large number of serious infections and related outcomes. METHODS: Data from the 2002 to 2012 National Inpatient Sample were analyzed, including an approximately 20% sample of all US hospitalizations (n = 72,108,077 adults)...
January 2018: Annals of Allergy, Asthma & Immunology
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