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Tuberculosis and immune response

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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/29324800/hepcidin-deficiency-and-iron-deficiency-do-not-alter-tuberculosis-susceptibility-in-a-murine-m-tb-infection-model
#3
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
#4
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/29321691/deciphering-the-nature-of-the-coral-chromera-association
#5
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
#6
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
#7
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/29316047/parainfluenza-virus-5-vectored-vaccines-against-human-and-animal-infectious-diseases
#8
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
#9
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
#10
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
#11
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/29291452/ifn-%C3%AE-decreased-the-suppressive-function-of-cd33-hla-drlow-myeloid-cells-through-down-regulation-of-pd-1-pd-l2-signaling-pathway
#12
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/29259310/clinical-and-immunological-effects-of-rhil-2-therapy-in-eastern-chinese-patients-with-multidrug-resistant-tuberculosis
#13
Qi Tan, Rui Min, Guan-Qun Dai, Yan-Li Wang, Li Nan, Zhen Yang, Jun Xia, Shi-Yang Pan, Huang Mao, Wei-Ping Xie, Hong Wang
It is urgent to find an optimised therapy regimen for the control of MDR-TB globally. This study aimed to evaluate the efficiacy and safety of a combined regimen of rhIL-2 injection and standard chemotherapy within 18-month duration in a randomized controlled trial conducted in 14 centres in eastern China. From Jan. 2009 to July. 2016, 271 MDR-TB cases were enrolled and followed up in two groups, 142 cases in study group while 129 cases in control group. Clinical efficacy, safety and immune activity (Th1, Th17, Treg, IFN-γ, IL-17) among the two groups were evaluated and compared...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29258402/pathology-of-the-emerging-mycobacterium-tuberculosis-complex-pathogen-mycobacterium-mungi-in-the-banded-mongoose-mungos-mungo
#14
Kathleen A Alexander, Peter N Laver, Mark C Williams, Claire E Sanderson, Carly Kanipe, Mitchell V Palmer
Wild banded mongooses ( Mungos mungo) in northeastern Botswana and northwest Zimbabwe are infected with a novel Mycobacterium tuberculosis complex (MTC) pathogen, Mycobacterium mungi. We evaluated gross and histologic lesions in 62 infected mongooses (1999-2017). Many tissues contained multifocal irregular, lymphohistiocytic to granulomatous infiltrates and/or multifocal or coalescing noncaseating to caseating granulomas with variable numbers of intralesional acid-fast bacilli. Over one-third of nasal turbinates examined had submucosal lymphohistiocytic to granulomatous infiltrates, erosion and ulceration of the nasal mucosa, bony remodeling, and nasal distortion...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/29258190/ifn-%C3%AE-a-contentious-player-in-host-pathogen-interaction-in-tuberculosis
#15
REVIEW
Naveed Sabir, Tariq Hussain, Syed Zahid Ali Shah, Deming Zhao, Xiangmei Zhou
Tuberculosis (TB) is a major health threat to the human population worldwide. The etiology of the disease is Mycobacterium tuberculosis (Mtb), a highly successful intracellular pathogen. It has the ability to manipulate the host immune response and to make the intracellular environment suitable for its survival. Many studies have addressed the interactions between the bacteria and the host immune cells as involving many immune mediators and other cellular players. Interferon-β (IFN-β) signaling is crucial for inducing the host innate immune response and it is an important determinant in the fate of mycobacterial infection...
December 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29249639/t-cells-primed-by-live-mycobacteria-versus-a-tuberculosis-subunit-vaccine-exhibit-distinct-functional-properties
#16
Thomas Lindenstrøm, Albanus Moguche, Mie Damborg, Else Marie Agger, Kevin Urdahl, Peter Andersen
Despite inducing strong T cell responses, Mycobacterium tuberculosis (Mtb) infection fails to elicit protective immune memory. As such latently infected or successfully treated Tuberculosis (TB) patients are not protected against recurrent disease. Here, using a mouse model of aerosol Mtb infection, we show that memory immunity to H56/CAF01 subunit vaccination conferred sustained protection in contrast to the transient natural immunity conferred by Mtb infection. Loss of protection to re-infection in natural Mtb memory was temporally linked to an accelerated differentiation of ESAT-6- and to a lesser extent, Ag85B-specific CD4 T cells in both the lung parenchyma and vasculature...
December 7, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29245359/potential-killer-in-the-icu-severe-tuberculosis-combined-with-hemophagocytic-syndrome-a-case-series-and-literature-review
#17
Lulu Chen, Heng Weng, Hongyan Li, Jinbao Huang, Jianguang Pan, Yansheng Huang, Chenhui Ma
Hemophagocytic syndrome (HPS) is a life-threatening clinical syndrome that has various presentations, shows rapid progression and is associated with a high mortality. Clinical reports about pulmonary tuberculosis combined with respiratory failure accompanied by HPS are rare.HPS has no special clinical manifestations, and the main presentations include persistent fever, hepatosplenomegaly, hematocytopenia, and rash. In the Intensive Care Unit (ICU), the clinical manifestations of severe infection and secondary HPS overlap, thus there is often a delay in the diagnosis and treatment of HPS...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29243495/the-recombinant-fusion-protein-cfp10-esat6-difn-has-protective-effect-against-tuberculosis-in-guinea-pigs
#18
Natalya V Permyakova, Pavel A Belavin, Dariya S Pirozhkova, Elena G Ufimtseva, Sergey M Rozov, Sergey R Mursalimov, Yuriy V Sidorchuk, Elena A Uvarova, Alla A Zagorskaya, Tatiana V Marenkova, Svetlana V Bannikova, Evgeniy A Demidov, Konstantin V Starostin, Marionella A Kravchenko, Diana V Vakhrusheva, Roman B Berdnikov, Natalya I Eremeeva, Sergey N Skornyakov, Sergey E Peltek, Elena V Deineko
Development of effective vaccine candidates against tuberculosis (TB) is currently the most important challenge in the prevention of this disease since the BCG vaccine fails to guarantee a lifelong protection, while any other approved vaccine with better efficiency is still absent. The protective effect of the recombinant fusion protein CFP10-ESAT6-dIFN produced in a prokaryotic expression system (Escherichia coli) has been assessed in a guinea pig model of acute TB. The tested antigen comprises the Mycobacterium tuberculosis (Mtb) proteins ESAT6 and CFP10 as well as modified human γ-interferon (dIFN) for boosting the immune response...
December 15, 2017: Acta Microbiologica et Immunologica Hungarica
https://www.readbyqxmd.com/read/29242831/novel-concepts-for-hiv-vaccine-vector-design
#19
REVIEW
Quazim A Alayo, Nicholas M Provine, Pablo Penaloza-MacMaster
The unprecedented challenges of developing effective vaccines against intracellular pathogens such as HIV, malaria, and tuberculosis have resulted in more rational approaches to vaccine development. Apart from the recent advances in the design and selection of improved epitopes and adjuvants, there are also ongoing efforts to optimize delivery platforms. Viral vectors are the best-characterized delivery tools because of their intrinsic adjuvant capability, unique cellular tropism, and ability to trigger robust adaptive immune responses...
November 2017: MSphere
https://www.readbyqxmd.com/read/29242190/the-rv2633c-protein-of-mycobacterium-tuberculosis-is-a-non-heme-di-iron-catalase-with-a-possible-role-in-defenses-against-oxidative-stress
#20
Zhongxin Ma, Kyle T Strickland, Michelle D Cherne, Esha Sehanobish, Kyle H Rohde, William T Self, Victor L Davidson
The Rv2633c gene in Mycobacterium tuberculosis is rapidly upregulated after macrophage infection, suggesting that Rv2633c is involved in M. tuberculosis pathogenesis. However, the activity and role of the Rv2633c protein in host colonization is unknown. Here, we analyzed the Rv2633c protein sequence, which revealed the presence of an HHE cation-binding domain common in hemerythrin-like proteins. Phylogenetic analysis indicated that Rv2633c is a member of a distinct subset of hemerythrin-like proteins exclusive to mycobacteria...
December 14, 2017: Journal of Biological Chemistry
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