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https://www.readbyqxmd.com/read/28646367/ifn%C3%AE-producing-cd4-t-lymphocytes-the-double-edged-swords-in-tuberculosis
#1
Pawan Kumar
IFNγ-producing CD4(+) T cells (IFNγ(+)CD4(+) T cells) are the key orchestrators of protective immunity against Mycobacterium tuberculosis (Mtb). Primarily, these cells act by enabling Mtb-infected macrophages to enforce phagosome-lysosome fusion, produce reactive nitrogen intermediates (RNIs), and activate autophagy pathways. However, TB is a heterogeneous disease and a host of clinical and experimental findings has also implicated IFNγ(+)CD4(+) T cells in TB pathogenesis. High frequency of IFNγ(+)CD4(+) T cells is the most invariable feature of the active disease...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28642632/mcl-plays-an-anti-inflammatory-role-in-mycobacterium-tuberculosis-induced-immune-response-by-inhibiting-nf-%C3%AE%C2%BAb-and-nlrp3-inflammasome-activation
#2
Qingwen Zhang, Xinru Jiang, Weigang He, Kailin Wei, Jinxia Sun, Xiangyang Qin, Yuejuan Zheng, Xin Jiang
Mycobacterium tuberculosis (Mtb) remains a significant menace to global health as it induces granulomatous lung lesions and systemic inflammatory responses during active tuberculosis (TB). Micheliolide (MCL), a sesquiterpene lactone, was recently reported to have a function of relieving LPS-induced inflammatory response, but the regulative role of MCL on the immunopathology of TB still remains unknown. In this experiment, we examined the inhibitory effect of MCL on Mtb-induced inflammatory response in mouse macrophage-like cell line Raw264...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28636635/microrna-144-3p-inhibits-autophagy-activation-and-enhances-bacillus-calmette-gu%C3%A3-rin-infection-by-targeting-atg4a-in-raw264-7-macrophage-cells
#3
Le Guo, Linlin Zhou, Qian Gao, Aijun Zhang, Jun Wei, Dantong Hong, Yuankui Chu, Xiangguo Duan, Ying Zhang, Guangxian Xu
MicroRNAs (miRNAs) are small noncoding nucleotides that play major roles in the response of host immune cells. Autophagy plays a key role in activating the antimicrobial host defense against Mycobacterium tuberculosis (M. tuberculosis). Whether miRNAs specifically influence the activation of macrophage autophagy during M. tuberculosis infection is largely unknown. In the present study, we demonstrate that Mycobacterium bovis Bacillus Calmette-Guérin (BCG) infection of macrophages leads to increased expression of miR-144-3p, which targets autophagy-related gene 4a (ATG4a), to inhibit autophagy activation and antimicrobial responses to BCG...
2017: PloS One
https://www.readbyqxmd.com/read/28634479/whole-blood-profiling-of-bacillus-calmette-gu%C3%A3-rin-induced-trained-innate-immunity-in-infants-identifies-epidermal-growth-factor-il-6-platelet-derived-growth-factor-ab-bb-and-natural-killer-cell-activation
#4
Steven G Smith, Johanneke Kleinnijenhuis, Mihai G Netea, Hazel M Dockrell
Vaccination of infants with bacillus Calmette-Guérin (BCG) activates both the innate and adaptive arms of the immune response. The antimycobacterial effects of these responses most likely account for the ability of BCG to protect against childhood forms of tuberculosis (TB). There is also evidence for a heterologous protective effect of BCG vaccination against TB-unrelated mortality in low birth weight infants. A possible mechanism of action of this effect, the induction of trained innate immunity, has been demonstrated when cells from BCG-vaccinated adults are restimulated in vitro with non-related microbial stimuli...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28634401/ohrr-of-mycobacterium-smegmatis-senses-and-responds-to-intracellular-organic-hydroperoxide-stress
#5
Omar A Garnica, Kishore Das, Subramanian Dhandayuthapani
Organic hydroperoxide reductase regulator (OhrR) in bacteria is a sensor for organic hydroperoxide stress and a transcriptional regulator for the enzyme organic hydroperoxide reductase (Ohr). In this study we investigated, using a GFP reporter system, whether Mycobacterium smegmatis OhrR has the ability to sense and respond to intracellular organic hydroperoxide stress. It was observed that M. smegmatis strains bearing the pohr-gfpuv fusion construct were able to express GFP only in the absence of an intact ohrR gene, but not in its presence...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630063/listeria-vectored-vaccine-expressing-the-mycobacterium-tuberculosis-30-kda-major-secretory-protein-via-the-constitutively-active-prfa-regulon-boosts-bcg-efficacy-against-tuberculosis
#6
Qingmei Jia, Barbara Jane Dillon, Saša Masleša-Galić, Marcus A Horwitz
A potent vaccine against tuberculosis, one of the world's deadliest diseases, is needed to enhance the immunity of people worldwide, most of whom have been vaccinated with the partially effective BCG vaccine. Here we investigate novel live attenuated recombinant Listeria monocytogenes (rLm) vaccines expressing the Mycobacterium tuberculosis (Mtb) 30 kDa major secretory protein (r30/Ag85B) (rLm30) as heterologous booster vaccines in animals primed with BCG. Using three attenuated Lm vectors, rLm ΔactA (LmI), rLm ΔactA ΔinlB (LmII), and rLm ΔactA ΔinlBprfA* (LmIII), we constructed five rLm30 vaccine candidates expressing the r30 linked in-frame to the Lm Listeriolycin O signal sequence and driven by the hly promoter (h30) or linked in-frame to the ActA N-terminus and driven by the actA promoter (a30)...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28627635/concomitant-mycobacterium-tuberculosis-infection-promotes-lung-tumor-growth-through-enhancing-treg-development
#7
Yan Zhou, Zhangguo Hu, Shuhui Cao, Bo Yan, Jialin Qian, Hua Zhong
Lung cancer is the most common malignancy in humans. An increased population of CD4+Foxp3+ regulatory T cells (Tregs) in the tumor-associated microenvironment plays an important role in cancer immune evasion. The exact role and the involved mechanisms of concomitant H37Rv infection in non-small cell lung cancer (NSCLC) development are still not clear. Here, we showed that H37Rv infection promoted NSCLC cell growth with a higher percentage of Tregs found in draining lymph nodes. We also determined in vitro that H37Rv infection induced macrophage maturation and PD-L1 expression, which promoted Treg proportion, with enhanced proliferation suppression function...
June 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28620394/vitamin-d-counteracts-mycobacterium-tuberculosis-induced-cathelicidin-downregulation-in-dendritic-cells-and-allows-th1-differentiation-and-ifn%C3%AE-secretion
#8
Anna K O Rode, Martin Kongsbak, Marie M Hansen, Daniel Villalba Lopez, Trine B Levring, Anders Woetmann, Niels Ødum, Charlotte M Bonefeld, Carsten Geisler
Tuberculosis (TB) presents a serious health problem with approximately one-third of the world's population infected with Mycobacterium tuberculosis in a latent state. Experience from the pre-antibiotic era and more recent clinical studies have established a beneficial role of sunlight and vitamin D in patients with TB. At the same time, experimental data have shown that Th1 cells through production of IFNγ are crucial for cathelicidin release by macrophages, bacterial killing, and containment of M. tuberculosis in granulomas...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28616288/decreased-expression-of-perforin-in-cd8-t-lymphocytes-in-patients-with-mycobacterium-tuberculosis-infection-and-its-potential-value-as-a-marker-for-efficacy-of-treatment
#9
Hongbin Jiang, Huili Gong, Qing Zhang, Jin Gu, Li Liang, Jun Zhang
BACKGROUND: Cytolytic activity against mycobacteria tuberculosis (MTB) within the infected macrophage is a crucial step in the immunity against TB infection, as MTB is an intracellular bacterium. Cytotoxic molecules such as perforin and granzymes produced by cytolytic T cells directly participate in this process. In this study, we evaluated the cytotoxicity function employing flow cytometry analysis of the level of expression of interferon-γ (IFN-γ), perforin and granzyme B in CD8(+) T cells from patients with active pulmonary TB (PTB), stable PTB and healthy controls, and explored whether MTB antigen (MTB Ag)-stimulated cytotoxic molecules would be useful for monitoring responses to anti-TB treatment...
May 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28611371/ohmyungsamycins-promote-antimicrobial-responses-through-autophagy-activation-via-amp-activated-protein-kinase-pathway
#10
Tae Sung Kim, Yern-Hyerk Shin, Hye-Mi Lee, Jin Kyung Kim, Jin Ho Choe, Ji-Chan Jang, Soohyun Um, Hyo Sun Jin, Masaaki Komatsu, Guang-Ho Cha, Han-Jung Chae, Dong-Chan Oh, Eun-Kyeong Jo
The induction of host cell autophagy by various autophagy inducers contributes to the antimicrobial host defense against Mycobacterium tuberculosis (Mtb), a major pathogenic strain that causes human tuberculosis. In this study, we present a role for the newly identified cyclic peptides ohmyungsamycins (OMS) A and B in the antimicrobial responses against Mtb infections by activating autophagy in murine bone marrow-derived macrophages (BMDMs). OMS robustly activated autophagy, which was essentially required for the colocalization of LC3 autophagosomes with bacterial phagosomes and antimicrobial responses against Mtb in BMDMs...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28606793/mir-20b-inhibits-mycobacterium-tuberculosis-induced-inflammation-in-the-lung-of-mice-through-targeting-nlrp3
#11
Jun Lou, Yongli Wang, Zhimin Zhang, Weiqiang Qiu
Tuberculosis (TB) is one of immune-related disorders. Although dysregulation of miRNAs has been implicated in innate and adaptive immune response, the specific effect of miR-20b on TB has not been documented. In this study, downregulation of miR-20b and upregulation of NLRP3 were observed in macrophages of TB patients, increased levels of inflammatory factors secretion were observed in serum of TB patients. Next, we established a TB mice model by using M. tuberculosis infection and intravenous injection of miR-20b mimic...
June 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28597814/killing-mycobacterium-tuberculosis-in-vitro-what-model-systems-can-teach-us
#12
Tracy L Keiser, Georgiana E Purdy
Tuberculosis is one of the most successful human diseases in our history due in large part to the multitude of virulence factors exhibited by the causative agent, Mycobacterium tuberculosis. Understanding the pathogenic nuances of this organism in the context of its human host is an ongoing topic of study facilitated by isolating cells from model organisms such as mice and non-human primates. However, M. tuberculosis is an obligate intracellular human pathogen, and disease progression and outcome in these model systems can differ from that of human disease...
June 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28596772/epigenetic-regulation-of-matrix-metalloproteinase-1-and-3-expression-in-mycobacterium-tuberculosis-infection
#13
Rachel C Moores, Sara Brilha, Frans Schutgens, Paul T Elkington, Jon S Friedland
In pulmonary tuberculosis (TB), the inflammatory immune response against Mycobacterium tuberculosis (Mtb) is associated with tissue destruction and cavitation, which drives disease transmission, chronic lung disease, and mortality. Matrix metalloproteinase (MMP)-1 is a host enzyme critical for the development of cavitation. MMP expression has been shown to be epigenetically regulated in other inflammatory diseases, but the importance of such mechanisms in Mtb-associated induction of MMP-1 is unknown. We investigated the role of changes in histone acetylation in Mtb-induced MMP expression using inhibitors of histone deacetylases (HDACs) and histone acetyltransferases (HAT), HDAC siRNA, promoter-reporter constructs, and chromatin immunoprecipitation assays...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28594940/the-introduction-of-mesenchymal-stromal-cells-induces-different-immunological-responses-in-the-lungs-of-healthy-and-m-tuberculosis-infected-mice
#14
Tatiana Nenasheva, Alexander Nikolaev, Daniar Diykanov, Anna Sukhanova, Evgenii Tcyganov, Alexander Panteleev, Irina Bocharova, Yana Serdyuk, Leonid Nezlin, Tatiana Radaeva, Nikolai Adrianov, Yuri Rubtsov, Irina Lyadova
Mesenchymal stromal cells (MSC) have strong immunomodulatory properties and therefore can be used to control inflammation and tissue damage. It was suggested recently that MSC injections can be used to treat multi-drug resistant tuberculosis (TB). However, MSC trafficking and immunomodulatory effects of MSC injections during Mycobacterium tuberculosis (Mtb) infection have not been studied. To address this issue we have analyzed MSC distribution in tissues and local immunological effects of MSC injections in Mtb infected and uninfected mice...
2017: PloS One
https://www.readbyqxmd.com/read/28592799/whib4-regulates-the-pe-ppe-gene-family-and-is-essential-for-virulence-of-mycobacterium-marinum
#15
Jing Wu, Huan-Wei Ru, Zhi-Hao Xiang, Jun Jiang, Yu-Chen Wang, Lu Zhang, Jun Liu
During the course of infection, pathogenic mycobacteria including Mycobacterium tuberculosis (M. tb) encounter host environments of variable oxygen tension, ranging from the hypoxic center of granulomas to the most oxygenated region in the lung cavities. Mycobacterial responses to changes of oxygen tension are critically related to infection outcomes, such as latency and reactivation. WhiB4 is an iron-sulfur containing transcription factor that is highly sensitive to oxygen exposure. In this study, we found that WhiB4 of Mycobacterium marinum (M...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592427/positron-emission-tomography-imaging-of-macaques-with-tuberculosis-identifies-temporal-changes-in-granuloma-glucose-metabolism-and-integrin-%C3%AE-4%C3%AE-1-expressing-immune-cells
#16
Joshua T Mattila, Wissam Beaino, Pauline Maiello, M Teresa Coleman, Alexander G White, Charles A Scanga, JoAnne L Flynn, Carolyn J Anderson
Positron emission tomography and computed tomography imaging (PET/CT) is an increasingly valuable tool for diagnosing tuberculosis (TB). The glucose analog [(18)F]fluoro-2-deoxy-2-d-glucose ([(18)F]-FDG) is commonly used in PET/CT that is retained by metabolically active inflammatory cells in granulomas, but lacks specificity for particular cell types. A PET probe that could identify recruitment and differentiation of different cell populations in granulomas would be a useful research tool and could improve TB diagnosis and treatment...
June 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28588573/bovine-wc1-and-wc1-neg-%C3%AE-%C3%AE-t-lymphocytes-influence-monocyte-differentiation-and-monocyte-derived-dendritic-cell-maturation-during-in-vitro-mycobacterium-avium-subspecies-paratuberculosis-infection
#17
Monica M Baquero, Brandon L Plattner
During early Mycobacterium avium subspecies paratuberculosis (Map) infection, complex interactions occur between the bacteria, cells from the mononuclear phagocyte system (MPS) including both resident (macrophages and dendritic cells) and recruited (monocytes) cells, and other mucosal sentinel cells such as γδ T lymphocytes. Though the details of early host-pathogen interactions in cattle remain largely underexplored, our hypothesis is that these significantly influence development of host immunity and ultimate success or failure of the host to respond to Map infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28574259/targeting-mycolic-acid-transport-by-indole-2-carboxamides-for-the-treatment-of-mycobacterium-abscessus-infections
#18
Alan P Kozikowski, Oluseye K Onajole, Jozef Stec, Christian Dupont, Albertus Viljoen, Matthias Richard, Tridib Chaira, Shichun Lun, William Bishai, V Samuel Raj, Diane Ordway, Laurent Kremer
Mycobacterium abscessus is a fast-growing, multidrug-resistant organism that has emerged as a clinically significant pathogen in cystic fibrosis (CF) patients. The intrinsic resistance of M. abscessus to most commonly available antibiotics seriously restricts chemotherapeutic options. Herein, we report the potent activity of a series of indolecarboxamides against M. abscessus. The lead compounds, 6 and 12, exhibited strong activity in vitro against a wide panel of M. abscessus isolates and in infected macrophages...
June 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28573139/analysis-of-differentially-expressed-proteins-in-mycobacterium-avium-infected-macrophages-comparing-with-mycobacterium-tuberculosis-infected-macrophages
#19
Dongjun Yang, Xin Fu, Shiyi He, Xueping Ning, Min Ling
Mycobacterium avium (MA) belongs to the intracellular parasitic bacteria. To better understand how MA survives within macrophages and the different pathogenic mechanisms of MA and Mycobacterium tuberculosis (MTB), tandem mass tag (TMT) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis have been used to determine the proteins which are differentially expressed in MA-infected and MTB-infected macrophages. 369 proteins were found to be differentially expressed in MA-infected cells but not in MTB-infected cells...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28570642/mycobacterium-tuberculosis-subverts-negative-regulatory-pathways-in-human-macrophages-to-drive-immunopathology
#20
Patience T Brace, Liku B Tezera, Magdalena K Bielecka, Toby Mellows, Diana Garay, Shuye Tian, Lucinda Rand, Justin Green, Sanjay Jogai, Andrew J Steele, Timothy M Millar, Tilman Sanchez-Elsner, Jon S Friedland, Christopher G Proud, Paul T Elkington
Tuberculosis remains a global pandemic and drives lung matrix destruction to transmit. Whilst pathways driving inflammatory responses in macrophages have been relatively well described, negative regulatory pathways are less well defined. We hypothesised that Mycobacterium tuberculosis (Mtb) specifically targets negative regulatory pathways to augment immunopathology. Inhibition of signalling through the PI3K/AKT/mTORC1 pathway increased matrix metalloproteinase-1 (MMP-1) gene expression and secretion, a collagenase central to TB pathogenesis, and multiple pro-inflammatory cytokines...
June 2017: PLoS Pathogens
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