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Tuberculosis and immune response

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https://www.readbyqxmd.com/read/28442574/the-r753q-polymorphism-in-toll-like-receptor-2-tlr2-attenuates-innate-immune-responses-to-mycobacteria-and-impairs-myd88-adapter-recruitment-to-tlr2
#1
Goutham Pattabiraman, Rahul Panchal, Andrei E Medvedev
Toll-like receptor (TLR) 2 plays a critical role in host defenses against mycobacterial infections. The Arg753Gln (R753Q) TLR2 polymorphism has been associated with increased incidence of tuberculosis and infections with non-tuberculous mycobacteria in human populations, but the mechanisms by which this polymorphism affects TLR2 signaling are unclear. In this study, we determined the impact of the R753Q TLR2 polymorphism on macrophage sensing of Mycobacterium smegmatis. Upon infection with M. smegmatis, macrophages from knock-in (KI) mice harboring R753Q TLR2 expressed lower levels of TNF-α, IL-1β, IL-6 and IL-10 compared to cells from wild-type (WT) mice but both R753Q TLR2 and WT mice exhibited comparable bacterial burdens...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28440335/mycobacterium-tuberculosis-pe_pgrs41-enhances-the-intracellular-survival-of-m-smegmatis-within-macrophages-via-blocking-innate-immunity-and-inhibition-of-host-defense
#2
Wanyan Deng, Quanxin Long, Jie Zeng, Ping Li, Wenmin Yang, Xinchun Chen, Jianping Xie
The success of Mycobacterium tuberculosis (M. tuberculosis) as a pathogen is largely contributes to its ability to manipulate the host immune responses. The genome of M. tuberculosis encodes multiple immune-modulatory proteins, including several members of the multi-genic PE_PPE family. Despite of intense research, the roles of PE_PGRS proteins in mycobacterial pathogenesis remain elusive. The function of M. tuberculosis PE_PGRS41, characterized by an extended and unique C-terminal domain, was studied. Expression of PE_PGRS41 in Mycobacterium smegmatis, a non-pathogenic species intrinsically deficient of PE_PGRS, severely impaired the resistance of the recombinant to multiple stresses via altering the cell wall integrity...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28438994/latently-and-uninfected-healthcare-workers-exposed-to-tb-make-protective-antibodies-against-mycobacterium-tuberculosis
#3
Hao Li, Xing-Xing Wang, Bin Wang, Lei Fu, Guan Liu, Yu Lu, Min Cao, Hairong Huang, Babak Javid
The role of Igs in natural protection against infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB, is controversial. Although passive immunization with mAbs generated against mycobacterial antigens has shown protective efficacy in murine models of infection, studies in B cell-depleted animals only showed modest phenotypes. We do not know if humans make protective antibody responses. Here, we investigated whether healthcare workers in a Beijing TB hospital-who, although exposed to suprainfectious doses of pathogenic Mtb, remain healthy-make antibody responses that are effective in protecting against infection by Mtb...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28436493/an-attenuated-mycobacterium-tuberculosis-clinical-strain-with-a-defect-in-esx-1-secretion-induces-minimal-host-immune-responses-and-pathology
#4
Helena Strand Clemmensen, Niels Peter Hell Knudsen, Erik Michael Rasmussen, Jessica Winkler, Ida Rosenkrands, Ahmad Ahmad, Troels Lillebaek, David R Sherman, Peter Lawætz Andersen, Claus Aagaard
Although Mycobacterium tuberculosis (M.tb) DK9897 is an attenuated strain, it was isolated from a patient with extrapulmonary tuberculosis and vaccination with a subunit vaccine (H56) induced poor protection against it. Both attenuation and lack of protection are because M.tb DK9897 cannot secrete the EsxA virulence factor nor induce a host response against it. Genome sequencing identified a frameshift mutation in the eccCa1 gene. Since the encoded EccCa1 protein provides energy for ESX-1 secretion, it suggested a defect in the ESX-1 type VII secretion system...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28431845/infection-prevention-and-control-and-the-refugee-population-experiences-from-the-university-of-louisville-global-health-center
#5
Ruth M Carrico, Linda Goss, Timothy L Wiemken, Rahel S Bosson, Paula Peyrani, William A Mattingly, Allison Pauly, Rebecca A Ford, Stanley Kotey, Julio A Ramirez
BACKGROUND: During 2016, approximately 140,000 individuals entered the United States as part of the federal government refugee resettlement program and established themselves in communities in virtually every state. No national database regarding refugee health currently exists; therefore, little is known about existing infectious diseases, conditions, and cultural practices that impact successful acculturation. The objective of this report is to identify what is currently known about refugees and circumstances important to infection prevention and control with respect to their roles as new community members, employees, and consumers of health care...
April 18, 2017: American Journal of Infection Control
https://www.readbyqxmd.com/read/28429162/involvement-of-methylated-hbha-expressed-from-mycobacterium-smegmatis-in-an-ifn-%C3%AE-release-assay-to-aid-discrimination-between-latent-infection-and-active-tuberculosis-in-bcg-vaccinated-populations
#6
H-L Wen, C-L Li, G Li, Y-H Lu, H-C Li, T Li, H-M Zhao, K Wu, D B Lowrie, J-X Lv, S-H Lu, X-Y Fan
IFN-γ release assays (IGRAs) based on region of difference 1 (RD1) antigens have improved diagnosis of Mycobacterium tuberculosis (M. tb) infection. However, IGRAs with these antigens cannot discriminate between active tuberculosis (ATB) and latent tuberculosis infection (LTBI). M. tb heparin-binding-hemagglutinin (HBHA) induces relatively high IFN-γ responses in LTBI individuals and low responses in ATB patients, but purification of the native methylated HBHA from cultures of M. tb for immunological tests is complex and time-consuming...
April 20, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28428627/glucocorticoids-suppress-antimicrobial-autophagy-and-nitric-oxide-production-and-facilitate-mycobacterial-survival-in-macrophages
#7
Jinli Wang, Ruining Wang, Hui Wang, Xiaofan Yang, Jiahui Yang, Wenjing Xiong, Qian Wen, Li Ma
Chronic administration of glucocorticoids has been shown to render individuals highly susceptible to mycobacterial infection and lead to reactivation of latent bacilli. However, the effect of glucocorticoids on innate anti-mycobacterial defense, especially in macrophages remains largely unknown. Here, we found that glucocorticoids inhibited the innate immune response, antimicrobial nitric oxide production and autophagy in mycobacteria-challenged macrophages. Meanwhile, maturation and acidification of mycobacterial phagosomes were attenuated in RAW264...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428201/dihydrolipoamide-dehydrogenase-lpd-rv0462-specific-t-cell-recall-responses-are-higher-in-healthy-household-contacts-of-tb-a-novel-immunodominant-antigen-from-m-tuberculosis
#8
Santhi Devasundaram, Alamelu Raja
The partial effectiveness against pulmonary tuberculosis (PTB), displayed by the existing tuberculosis (TB) vaccine, bacillus Calmette-Guérin (BCG), highlights the need for novel vaccines to replace or improve BCG. In TB immunology, antigen-specific cellular immune response is frequently considered indispensable. Latency-associated antigens are intriguing as targets for TB vaccine development. The mycobacterial protein, dihydrolipoamide dehydrogenase (Lpd; Rv0462), the third enzyme of the pyruvate dehydrogenase (PDH) complex, facilitates Mycobacterium tuberculosis to resist host reactive nitrogen intermediates...
April 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28426273/preclinical-development-of-bcg-hiva-2auxo-int-harboring-an-integrative-expression-vector-for-a-hiv-tb-pediatric-vaccine-enhancement-of-stability-and-specific-hiv-1-t-cell-immunity
#9
Aakash Mahant, Narcís Saubi, Yoshiki Eto, Núria Guitart, Josep M ª Gatell, Tomáš Hanke, Joan Joseph
One of the critical issues that should be addressed in the development of a BCG-based HIV vaccine is genetic plasmid stability. Therefore, to address this issue we have considered using integrative vectors and the auxotrophic mutant of BCG complemented with a plasmid carrying a wild-type complementing gene. In this study, we have constructed an integrative E. coli-mycobacterial shuttle plasmid, p2auxo.HIVA(int), expressing the HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism for plasmid selection and maintenance...
April 20, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28424703/immune-responses-to-bacillus-calmette-gu%C3%A3-rin-vaccination-why-do-they-fail-to-protect-against-mycobacterium-tuberculosis
#10
REVIEW
Juan I Moliva, Joanne Turner, Jordi B Torrelles
Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis (TB), is the current leading cause of death due to a single infectious organism. Although curable, the broad emergence of multi-, extensive-, extreme-, and total-drug resistant strains of M.tb has hindered eradication efforts of this pathogen. Furthermore, computational models predict a quarter of the world's population is infected with M.tb in a latent state, effectively serving as the largest reservoir for any human pathogen with the ability to cause significant morbidity and mortality...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28424682/interactions-between-type-1-interferons-and-the-th17-response-in-tuberculosis-lessons-learned-from-autoimmune-diseases
#11
REVIEW
Bas C Mourik, Erik Lubberts, Jurriaan E M de Steenwinkel, Tom H M Ottenhoff, Pieter J M Leenen
The classical paradigm of tuberculosis (TB) immunity, with a central protective role for Th1 responses and IFN-γ-stimulated cellular responses, has been challenged by unsatisfactory results of vaccine strategies aimed at enhancing Th1 immunity. Moreover, preclinical TB models have shown that increasing IFN-γ responses in the lungs is more damaging to the host than to the pathogen. Type 1 interferon signaling and altered Th17 responses have also been associated with active TB, but their functional roles in TB pathogenesis remain to be established...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28410676/the-immunoregulatory-effects-of-co-infection-with-fasciola-hepatica-from-bovine-tuberculosis-to-johne-s-disease
#12
REVIEW
Amalia Naranjo Lucena, Laura Garza Cuartero, Grace Mulcahy, Annetta Zintl
Fasciola hepatica (liver fluke) is a parasite prevalent in much of the world that causes the economically-important disease of fasciolosis in livestock. The threat that this disease poses extends beyond its direct effects due to the parasite's immunomodulatory effects. Research at this laboratory is focusing on whether this immunoregulation can, in animals infected with liver fluke, exert a bystander effect on concurrent infections in the host. It has already been established that F. hepatica infection reduces cell mediated immune responses to Mycobacterium bovis in cattle, and that the interaction between the two pathogens can be detected on an epidemiological scale...
April 2017: Veterinary Journal
https://www.readbyqxmd.com/read/28404571/early-detection-of-circulating-antigen-and-igm-associated-immune-complexes-during-experimental-mycobacterium-bovis-infection-in-cattle
#13
Konstantin P Lyashchenko, Rena Greenwald, Alina Sikar-Gang, Archana A Sridhara, Ashley Johnathan, Paul Lambotte, Javan Esfandiari, Mayara F Maggioli, Tyler C Thacker, Mitchell V Palmer, W Ray Waters
The presence of circulating antigen in cattle experimentally infected with Mycobacterium bovis was demonstrated using dual-path platform (DPP) technology. The antigen-capture immunoassays employed rabbit polyclonal antibody recognizing predominantly M. tuberculosis complex-specific epitopes and were able to detect soluble substances and whole cells of mycobacteria. The antigen found in serum appeared to be mostly bound to IgM, but not to IgG, within the immune complexes formed at early stages of M. bovis infection...
April 12, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28403225/association-of-vitamin-d-deficiency-season-of-the-year-and-latent-tuberculosis-infection-among-household-contacts
#14
María Elvira Balcells, Patricia García, Camila Tiznado, Luis Villarroel, Natalia Scioscia, Camila Carvajal, Francesca Zegna-Ratá, Mariluz Hernández, Paulina Meza, Luis F González, Carlos Peña, Rodrigo Naves
OBJECTIVES: Vitamin D (VD) enhances the immune response against Mycobacterium tuberculosis in vitro, and VD deficiency has been described in patients with active tuberculosis (TB). However, the role of hypovitaminosis D in the pathogenesis of early TB infection acquisition is unclear. We aimed to evaluate the association of VD deficiency, season of the year, and latent TB infection in household contacts (HHC), given that this is a potentially modifiable condition often related to nutritional deficiencies and lack of sun exposure...
2017: PloS One
https://www.readbyqxmd.com/read/28399967/type-1-polarised-dendritic-cells-are-a-potent-immunogen-against-mycobacterium-tuberculosis
#15
Y Satake, Y Nakamura, M Kono, H Hozumi, T Nagata, K Tsujimura, N Enomoto, T Fujisawa, N Inui, T Fujiyama, Y Tokura, T Matsui, K Yokomura, M Shirai, H Hayakawa, T Suda
OBJECTIVE: Application of immunotherapy using dendritic cells (DCs) is considered an effective treatment strategy against persistent Mycobacterium tuberculosis infection. With the goal of developing improved therapeutic vaccination strategies for patients with tuberculosis (TB), we tested the ability of ex vivo-generated DCs to induce an effective TB antigen-specific type-1 immune response. METHODS: Monocyte-derived DCs from TB patients were induced to mature using a 'standard' cytokine cocktail (interleukin [IL] 1β, tumour necrosis factor alpha [TNF-α], IL-6 and prostaglandin E2) or a type 1-polarised DC (DC1) cocktail (IL-1β, TNF-α, interferon [IFN] α, IFN-γ and polyinosinic:polycytidylic acid), and were loaded with the established TB antigen 6-kDa early secretory antigenic target protein (ESAT-6)...
May 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28393919/association-of-c-type-lectin-mincle-with-fc%C3%AE%C2%B5ri%C3%AE-%C3%AE-subunits-leads-to-functional-activation-of-rbl-2h3-cells-through-syk
#16
Chisato Honjoh, Kazuyasu Chihara, Hatsumi Yoshiki, Shota Yamauchi, Kenji Takeuchi, Yuji Kato, Yukio Hida, Tamotsu Ishizuka, Kiyonao Sada
Macrophage-inducible C-type lectin (Mincle) interacts with the γ-subunit of high-affinity IgE receptor (FcεRIγ) and activates Syk by recognizing its specific ligand, trehalose-6,6'-dimycolate, a glycolipid produced by Mycobacterium tuberculosis. It has been suggested that mast cells participate in the immune defense against pathogenic microbes including M. tuberculosis, although the functions are still uncertain. In this study, we examined the Mincle-mediated signaling pathway and cellular responses using RBL-2H3 cells...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28393466/improving-basic-and-membrane-protein-ms-detection-of-the-culture-filtrate-proteins-from-mycobacterium-tuberculosis-h37rv-by-biomimetic-affinity-pre-fractionation
#17
Guorong Ma, Fuqiang Zhou, Lina Gao, Zhanqiang Sun, Li Deng, Shulin Zhang, Rongxiu Li
The culture filtrate proteins (CFPs) from Mycobacterium tuberculosis (MTB) have been shown to induce protective immune responses in human and animal models, making them a promising source of candidate targets for tuberculosis drugs, vaccines and diagnostics. The constituents of the MTB CFP proteome are complex and vary with growth conditions. To effectively profile CFPs, gel-based pre-fractionation is usually performed before MS analysis. In this study, we describe a novel pre-fractionation approach by which the proteome is divided into seven partially overlapping fractions by biomimetic affinity chromatography (BiAC) using a six-column cascade...
April 9, 2017: Proteomics
https://www.readbyqxmd.com/read/28393361/immune-checkpoints-and-their-inhibition-in-cancer-and-infectious-diseases
#18
REVIEW
Lydia Dyck, Kingston H G Mills
The development of chronic infections and cancer is facilitated by a variety of immune subversion mechanisms, such as the production of anti-inflammatory cytokines, induction of regulatory T (Treg) cells, and expression of immune checkpoint molecules, including CTLA-4 and PD-1. CTLA-4, expressed on T cells, interacts with CD80/CD86, thereby limiting T-cell activation and leading to anergy. PD-1 is predominantly expressed on T cells and its interaction with PD-L1 and PD-L2 expressed on antigen-presenting cells (APCs) and tumors sends a negative signal to T cells, which can lead to T-cell exhaustion...
April 9, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28384290/mait-cells-are-reduced-in-frequency-and-functionally-impaired-in-human-t-lymphotropic-virus-type-1-infection-potential-clinical-implications
#19
Dominic Paquin-Proulx, Benjamin C Greenspun, Emanuela A S Costa, Aluisio C Segurado, Esper G Kallas, Douglas F Nixon, Fabio E Leal
HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develop HAM/TSP. The cellular immune response has been implicated in the development of inflammatory alterations in these patients; however the pathogenic mechanisms for disease progression remain unclear. Furthermore, HTLV-1-infected individuals have an increase incidence of Mycobacterium tuberculosis (Mtb) infection, suggesting that immunological defect are associated with HTLV-1 infection...
2017: PloS One
https://www.readbyqxmd.com/read/28382943/badger-macrophages-fail-to-produce-nitric-oxide-a-key-anti-mycobacterial-effector-molecule
#20
Kirstin Bilham, Amy C Boyd, Stephen G Preston, Christina D Buesching, Chris Newman, David W Macdonald, Adrian L Smith
The European badger is recognised as a wildlife reservoir for bovine tuberculosis (bTB); the control of which is complex, costly and controversial. Despite the importance of badgers in bTB and the well-documented role for macrophages as anti-mycobacterial effector cells, badger macrophage (bdMφ) responses remain uncharacterised. Here, we demonstrate that bdMφ fail to produce nitric oxide (NO) or upregulate inducible nitric oxide synthase (iNOS) mRNA following Toll-like receptor (TLR) agonist treatment. BdMφ also failed to make NO after stimulation with recombinant badger interferon gamma (bdIFNγ) or a combination of bdIFNγ and lipopolysaccharide...
April 6, 2017: Scientific Reports
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