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Tuberculosis immunity

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https://www.readbyqxmd.com/read/29793057/ellagic-acid-protects-from-myelin-associated-sphingolipid-loss-in-experimental-autoimmune-encephalomyelitis
#1
Rebeca Busto, Jorge Serna, Aránzazu Perianes-Cachero, Rocío Quintana-Portillo, David García-Seisdedos, Alberto Canfrán-Duque, Carlos L Paino, Milagros Lerma, María E Casado, Antonia Martín-Hidalgo, Eduardo Arilla-Ferreiro, Miguel A Lasunción, Óscar Pastor
Experimental autoimmune encephalomyelitis (EAE), the most common model for multiple sclerosis, is characterized by inflammatory cell infiltration into the central nervous system and demyelination. Previous studies have demonstrated that administration of some polyphenols may reduce the neurological alterations of EAE. In this work, we show that ellagic acid, a polyphenolic compound, is beneficial in EAE, most likely through stimulation of ceramide biosynthesis within the brain. EAE was induced in Lewis rats by injection of guinea-pig spinal cord tissue along with Freund's complete adjuvant containing Mycobacterium tuberculosis...
May 21, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29791904/the-cgas-sting-pathway-is-important-for-dendritic-cell-activation-but-is-not-essential-to-induce-protective-immunity-against-mycobacterium-tuberculosis-infection
#2
Fabio V Marinho, Sulayman Benmerzoug, Stephanie Rose, Priscila C Campos, João T Marques, André Báfica, Glen Barber, Bernhard Ryffel, Sergio C Oliveira, Valerie F J Quesniaux
Mycobacterium tuberculosis (Mtb) infection remains a major public health concern. The STING (stimulator of interferon genes) pathway contributes to the cytosolic surveillance of host cells. Most studies on the role of STING activation in Mtb infection have focused on macrophages. Moreover, a detailed investigation of the role of STING during Mtb infection in vivo is required. Here, we deciphered the involvement of STING in the activation of dendritic cells (DCs) and the host response to Mtb infection in vivo...
May 23, 2018: Journal of Innate Immunity
https://www.readbyqxmd.com/read/29789389/lrrk2-is-a-negative-regulator-of-mycobacterium-tuberculosis-phagosome-maturation-in-macrophages
#3
Anetta Härtlova, Susanne Herbst, Julien Peltier, Angela Rodgers, Orsolya Bilkei-Gorzo, Antony Fearns, Brian D Dill, Heyne Lee, Rowan Flynn, Sally A Cowley, Paul Davies, Patrick A Lewis, Ian G Ganley, Jennifer Martinez, Dario R Alessi, Alastair D Reith, Matthias Trost, Maximiliano G Gutierrez
Mutations in the leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson's disease, chronic inflammation and mycobacterial infections. Although there is evidence supporting the idea that LRRK2 has an immune function, the cellular function of this kinase is still largely unknown. By using genetic, pharmacological and proteomics approaches, we show that LRRK2 kinase activity negatively regulates phagosome maturation via the recruitment of the Class III phosphatidylinositol-3 kinase complex and Rubicon to the phagosome in macrophages...
May 22, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29787561/interplay-of-strain-and-race-ethnicity-in-the-innate-immune-response-to-m-tuberculosis
#4
P Nahid, L G Jarlsberg, M Kato-Maeda, M R Segal, D H Osmond, S Gagneux, K Dobos, M Gold, P C Hopewell, D M Lewinsohn
BACKGROUND: The roles of host and pathogen factors in determining innate immune responses to M. tuberculosis are not fully understood. In this study, we examined host macrophage immune responses of 3 race/ethnic groups to 3 genetically and geographically diverse M. tuberculosis lineages. METHODS: Monocyte-derived macrophages from healthy Filipinos, Chinese and non-Hispanic White study participants (approximately 45 individuals/group) were challenged with M. tuberculosis whole cell lysates of clinical strains Beijing HN878 (lineage 2), Manila T31 (lineage 1), CDC1551 (lineage 4), the reference strain H37Rv (lineage 4), as well as with Toll-like receptor 2 agonist lipoteichoic acid (TLR2/LTA) and TLR4 agonist lipopolysaccharide (TLR4/LPS)...
2018: PloS One
https://www.readbyqxmd.com/read/29785902/milk-microrna-146a-as-a-potential-biomarker-in-bovine-tuberculosis
#5
Marco Iannaccone, Gianfranco Cosenza, Alfredo Pauciullo, Francesca Garofalo, Yolande T Proroga, Federico Capuano, Rosanna Capparelli
In this research communication we exploited the potential use of milk microRNAs (miRs) as biomarkers for bovine tuberculosis (bTB). bTB is a zoonotic disease caused by Mycobacterium bovis which affects animal health, influencing herd economic sustainability. Diagnosis is based on skin delayed-type hypersensitivity reaction and quantification of interferon gamma but both techniques are influenced by several confounding factors. Thus, new methods for early diagnosis are required. In this context, microRNAs have been used as promising biomarkers for both infectious and non-infectious diseases...
May 2018: Journal of Dairy Research
https://www.readbyqxmd.com/read/29782535/mycobacterium-tuberculosis-specific-cd4-and-cd8-t-cells-differ-in-their-capacity-to-recognize-infected-macrophages
#6
Jason D Yang, Daniel Mott, Rujapak Sutiwisesak, Yu-Jung Lu, Fiona Raso, Britni Stowell, Greg Hunter Babunovic, Jinhee Lee, Steve M Carpenter, Sing Sing Way, Sarah M Fortune, Samuel M Behar
Containment of Mycobacterium tuberculosis (Mtb) infection requires T cell recognition of infected macrophages. Mtb has evolved to tolerate, evade, and subvert host immunity. Despite a vigorous and sustained CD8+ T cell response during Mtb infection, CD8+ T cells make limited contribution to protection. Here, we ask whether the ability of Mtb-specific T cells to restrict Mtb growth is related to their capacity to recognize Mtb-infected macrophages. We derived CD8+ T cell lines that recognized the Mtb immunodominant epitope TB10...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29781535/mir-1178-regulates-mycobacterial-survival-and-inflammatory-responses-in-mycobacterium-tuberculosis-infected-macrophages-partly-via-tlr4
#7
Ge Shi, Guofeng Mao, Kejie Xie, Dongdong Wu, Wei Wang
Tuberculosis is chronic respiratory infectious disease and is caused by the infection of Mycobacterium tuberculosis (M.tb). Macrophages play an important role in host immune response against M.tb infection, which is regulated by various factors, including microRNAs (miRNAs). The present study aimed to examine the in vitro functional role of miR-1178 in mycobacterial survival and inflammatory responses induced by M.tb infection in human macrophages. Our results showed that M.tb infection increased the expression of miR-1178 in human macrophages (HTP-1 and U937 cells) in a concentration- and time-dependent manner...
May 21, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29779777/interleukin-23-interleukin-17-axis-activated-by-mycobacterium-avium-complex-mac-is-attenuated-in-patients-with-mac-lung-disease
#8
Chin-Chung Shu, Jann-Yuan Wang, Ming-Fang Wu, Hsin-Chih Lai, Bor-Luen Chiang, Chong-Jen Yu
BACKGROUND: Mycobacterium avium complex (MAC)-lung disease (LD) is increasing in patients without human immunodeficiency virus infection. However, data on host vulnerability to MAC-related immune responses, and in particular the interleukin (IL)-23/IL-17 axis, are lacking. METHODS: We enrolled 50 patients with MAC-LD, 25 age-matched patients with tuberculosis (TB) and 25 controls. We measured levels of plasma cytokines, and studied IL-12/IL-17 responses in macrophage and lymphocyte activation to MAC...
May 2018: Tuberculosis
https://www.readbyqxmd.com/read/29779770/normalised-quantitative-polymerase-chain-reaction-for-diagnosis-of-tuberculosis-associated-uveitis
#9
Manas Ranjan Barik, Soveeta Rath, Rohit Modi, Rajkishori Rana, Mamatha M Reddy, Soumyava Basu
Polymerase chain reaction (PCR)-based diagnosis of tuberculosis-associated uveitis (TBU) in TB-endemic countries is challenging due to likelihood of latent mycobacterial infection in both immune and non-immune cells. In this study, we investigated normalised quantitative PCR (nqPCR) in ocular fluids (aqueous/vitreous) for diagnosis of TBU in a TB-endemic population. Mycobacterial copy numbers (mpb64 gene) were normalised to host genome copy numbers (RNAse P RNA component H1 [RPPH1] gene) in TBU (n = 16) and control (n = 13) samples (discovery cohort)...
May 2018: Tuberculosis
https://www.readbyqxmd.com/read/29779768/genetic-diversity-of-antigen-38-kda-in-mycobacterium-tuberculosis-strains-from-china
#10
Yingzhen Du, Hongxia Li, Xuebing Qin, Yan Wang, Zhijian Zhang, Geping Qu, Xiangqun Fang, Senyang Yu
We used 335 Mycobacterium tuberculosis strains from 2010 National Epidemiologic Survey for TB in China and performed comparative sequence analysis of 38 kDa gene after amplification. From the results, we found that there were 5.07% M.tuberculosis strains that demonstrated genetic diversity of 38 kDa in China, and 2.99% strains showed polymorphism of the 38 kDa antigen, and this may be the reason for changes in the antigen produced, which may in turn cause alterations of related functions, thereby allowing immune evasion...
May 2018: Tuberculosis
https://www.readbyqxmd.com/read/29779765/prolonged-intervals-during-mycobacterium-tuberculosis-subunit-vaccine-boosting-contributes-to-eliciting-immunity-mediated-by-central-memory-like-t-cells
#11
Chunxiang Bai, Juanjuan He, Hongxia Niu, Lina Hu, Yanping Luo, Xun Liu, Liang Peng, Bingdong Zhu
It is believed that central memory T cells (TCM ) provide long-term protection against tuberculosis (TB). However, the effects of TB subunit vaccine immunization schedule, especially the vaccination intervals, on T cell immune memory is still unclear. In this study, mice were immunized with fusion protein ESAT6-Ag85B-MPT64 (190-198)-Mtb8.4-Rv2626c (LT70) based subunit vaccine three times according to the following schedules: ① 0, 3rd and 6th week respectively (0-3-6w), ② 0, 4th and 12th week (0-4-12w), and ③ 0, 4th and 24th week (0-4-24w)...
May 2018: Tuberculosis
https://www.readbyqxmd.com/read/29774023/ferritin-h-deficiency-in-myeloid-compartments-dysregulates-host-energy-metabolism-and-increases-susceptibility-to-mycobacterium-tuberculosis-infection
#12
Vineel P Reddy, Krishna C Chinta, Vikram Saini, Joel N Glasgow, Travis D Hull, Amie Traylor, Fernanda Rey-Stolle, Miguel P Soares, Rajhmun Madansein, Md Aejazur Rahman, Coral Barbas, Kievershen Nargan, Threnesan Naidoo, Pratistadevi K Ramdial, James F George, Anupam Agarwal, Adrie J C Steyn
Iron is an essential factor for the growth and virulence of Mycobacterium tuberculosis ( Mtb) . However, little is known about the mechanisms by which the host controls iron availability during infection. Since ferritin heavy chain (FtH) is a major intracellular source of reserve iron in the host, we hypothesized that the lack of FtH would cause dysregulated iron homeostasis to exacerbate TB disease. Therefore, we used knockout mice lacking FtH in myeloid-derived cell populations to study Mtb disease progression...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29773644/bhlhe40-is-an-essential-repressor-of-il-10-during-mycobacterium-tuberculosis-infection
#13
Jeremy P Huynh, Chih-Chung Lin, Jacqueline M Kimmey, Nicholas N Jarjour, Elizabeth A Schwarzkopf, Tara R Bradstreet, Irina Shchukina, Oleg Shpynov, Casey T Weaver, Reshma Taneja, Maxim N Artyomov, Brian T Edelson, Christina L Stallings
The cytokine IL-10 antagonizes pathways that control Mycobacterium tuberculosis ( Mtb ) infection. Nevertheless, the impact of IL-10 during Mtb infection has been difficult to decipher because loss-of-function studies in animal models have yielded only mild phenotypes. We have discovered that the transcription factor basic helix-loop-helix family member e40 (Bhlhe40) is required to repress Il10 expression during Mtb infection. Loss of Bhlhe40 in mice results in higher Il10 expression, higher bacterial burden, and early susceptibility similar to that observed in mice lacking IFN-γ...
May 17, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29773170/iron-and-innate-antimicrobial-immunity-depriving-the-pathogen-defending-the-host
#14
REVIEW
Manfred Nairz, Stefanie Dichtl, Andrea Schroll, David Haschka, Piotr Tymoszuk, Igor Theurl, Günter Weiss
The acute-phase response is triggered by the presence of infectious agents and danger signals which indicate hazards for the integrity of the mammalian body. One central feature of this response is the sequestration of iron into storage compartments including macrophages. This limits the availability of this essential nutrient for circulating pathogens, a host defence strategy known as 'nutritional immunity'. Iron metabolism and the immune response are intimately linked. In infections, the availability of iron affects both the efficacy of antimicrobial immune pathways and pathogen proliferation...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29772011/induction-of-influenza-specific-local-cd8-t-cells-in-the-respiratory-tract-after-aerosol-delivery-of-vaccine-antigen-or-virus-in-the-babraham-inbred-pig
#15
Katie Tungatt, Garry Dolton, Sophie B Morgan, Meriem Attaf, Anna Fuller, Thomas Whalley, Johanneke D Hemmink, Emily Porter, Barbara Szomolay, Maria Montoya, John A Hammond, John J Miles, David K Cole, Alain Townsend, Mick Bailey, Pierre J Rizkallah, Bryan Charleston, Elma Tchilian, Andrew K Sewell
There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume...
May 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29770360/biomarkers-associated-with-death-after-initiating-treatment-for-tuberculosis-and-hiv-in-patients-with-very-low-cd-4-cells
#16
Fred R Sattler, Daniel Chelliah, Xingye Wu, Alejandro Sanchez, Michelle A Kendall, Evelyn Hogg, David Lagat, Umesh Lalloo, Valdilea Veloso, Diane V Havlir, Alan Landay
Background: The risk of short-term death for treatment naive patients dually infected with Mycobacterium tuberculosis and HIV may be reduced by early anti-retroviral therapy. Of those dying, mechanisms responsible for fatal outcomes are unclear. We hypothesized that greater malnutrition and/or inflammation when initiating treatment are associated with an increased risk for death. Methods: We utilized a retrospective case-cohort design among participants of the ACTG A5221 study who had baseline CD4 < 50 cells/mm3 ...
2018: Pathogens & Immunity
https://www.readbyqxmd.com/read/29769102/securitizing-hiv-aids-a-game-changer-in-state-societal-relations-in-china
#17
Catherine Yuk-Ping Lo
BACKGROUND: China has experienced unprecedented economic growth since the 1980s. Despite this impressive economic development, this growth exists side by side with the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and severe acute respiratory syndrome (SARS) crises and the persisting deficiencies in public health provision in China. Acknowledging the prevailing health problems, the Chinese government has encouraged the development of health non-governmental organizations (NGOs) to respond to the health challenges and address the gaps in public health provision of the government...
May 16, 2018: Globalization and Health
https://www.readbyqxmd.com/read/29765355/tuberculosis-the-disrupted-immune-endocrine-response-and-the-potential-thymic-repercussion-as-a-contributing-factor-to-disease-physiopathology
#18
REVIEW
Luciano D'Attilio, Natalia Santucci, Bettina Bongiovanni, María L Bay, Oscar Bottasso
Upon the pathogen encounter, the host seeks to ensure an adequate inflammatory reaction to combat infection but at the same time tries to prevent collateral damage, through several regulatory mechanisms, like an endocrine response involving the production of adrenal steroid hormones. Our studies show that active tuberculosis (TB) patients present an immune-endocrine imbalance characterized by an impaired cellular immunity together with increased plasma levels of cortisol, pro-inflammatory cytokines, and decreased amounts of dehydroepiandrosterone...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29762680/tuberculosis-and-the-art-of-macrophage-manipulation
#19
S Upadhyay, E Mittal, J A Philips
Macrophages are first-line responders against microbes. The success of Mycobacterium tuberculosis (Mtb) rests upon its ability to convert these antimicrobial cells into a permissive cellular niche. This is a remarkable accomplishment, as the antimicrobial arsenal of macrophages is extensive. Normally bacteria are delivered to an acidic, degradative lysosome through one of several trafficking pathways, including LC3-associated phagocytosis (LAP) and autophagy. Once phagocytozed, the bacilli are subjected to reactive oxygen and nitrogen species, and they induce the expression of proinflammatory cytokines, which serve to augment host responses...
June 1, 2018: Pathogens and Disease
https://www.readbyqxmd.com/read/29760437/cd82-hypomethylation-is-essential-for-tuberculosis-pathogenesis-via-regulation-of-runx1-rab5-22
#20
Hyun-Jung Koh, Ye-Ram Kim, Jae-Sung Kim, Jin-Seung Yun, Sojin Kim, Sun Young Kim, Kiseok Jang, Chul-Su Yang
The tumor suppressor gene CD82/KAI1 is a member of the tetraspanin superfamily and organizes various membrane-based processes. Mycobacterium tuberculosis (MTB) persists in host macrophages by interfering with phagolysosome biogenesis and inflammatory responses, but the role of CD82 in controlling the intracellular survival of pathogenic mycobacteria within macrophages remains poorly understood. In this study, we demonstrated that the virulent MTB strain H37Rv (MTB Rv) induced CD82 promoter hypomethylation, resulting in CD82 expression...
May 14, 2018: Experimental & Molecular Medicine
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