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Tuberculosis immunity

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https://www.readbyqxmd.com/read/28210262/morphoproteomic-guided-host-directed-therapy-for-tuberculosis
#1
Robert E Brown, Robert L Hunter, Shen-An Hwang
In an effort to develop more effective therapy for tuberculosis (TB), research efforts are looking toward host-directed therapy, reprograming the body's natural defenses to better control the infection. While significant progress is being made, the efforts are limited by lack of understanding of the pathology and pathogenesis of adult type TB disease. We have recently published evidence that the developing lesions in human lungs are focal endogenous lipid pneumonia that constitutes a region of local susceptibility in a person with strong systemic immunity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28209712/mycobacterium-tuberculosis-esxl-inhibit-mhc-ii-expression-by-promoting-hypermethylation-in-class-ii-transactivator-loci-in-macrophages
#2
Srabasti Sengupta, Saba Naz, Ishani Das, Abdul Ahad, Avinash Padhi, Sumanta Naik, Geetanjali Ganguli, Kaliprasad Patnaik, Sunil Kumar Raghav, Vinay Nandicoori, Avinash Sonawane
Mycobacterium tuberculosis (Mtb) is known to modulate the host immune responses to facilitate its persistence inside the host cells. One of the key mechanisms includes repression of class-II transactivator (CIITA) and MHC-II expression in infected macrophages. However, the precise mechanism of CIITA and MHC-II down-regulation is not well studied. Mtb 6-kDa early secretory antigenic target (ESAT-6) is a known potent virulence and antigenic determinant. Mtb genome encodes 23 such ESAT-6 family proteins. We herein report that Mtb and M...
February 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28209523/tb-iris-proteomic-analysis-of-in-vitro-pbmc-responses-to-mycobacterium-tuberculosis-and-response-modulation-by-dexamethasone
#3
Liam Bell, Janique M Peyper, Shaun Garnett, Rabecca Tadokera, Robert Wilkinson, Graeme Meintjes, Jonathan M Blackburn
Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) occurs in 8-54% of South African patients undergoing treatment for tuberculosis/human immunodeficiency virus co-infection. Improved TB-IRIS molecular pathogenesis understanding would enhance risk stratification, diagnosis, prognostication, and treatment. We assessed how TB-IRIS status and dexamethasone influence leukocyte proteomic responses to Mycobacterium tuberculosis (Mtb). Patient blood was obtained three weeks post-anti-retroviral therapy initiation...
February 13, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28209436/is-colombia-reaching-the-goals-on-infant-immunization-coverage-a-quantitative-survey-from-80-municipalities
#4
Javier Narváez, May Bibiana Osorio, Carlos Castañeda-Orjuela, Nelson Alvis Zakzuk, Natalia Cediel, Luz Ángela Chocontá-Piraquive, Fernando de La Hoz-Restrepo
OBJECTIVES: This study aimed to evaluate the coverage of the Colombian Expanded Program on Immunization among children less than 6years old, to evaluate the timeliness of immunization, to assess the coverage of newly introduced vaccines, and to identify factors associated with lack of immunization. METHODS: We conducted a cross-sectional survey in 80 municipalities of Colombia, using a two-stage cluster random sampling. We attempted to contact all children less than 6years old living in the sampled blocks, and asked their caregivers to provide immunization record cards...
February 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28206982/biocompatible-chitosan-nanoparticles-as-an-efficient-delivery-vehicle-for-mycobacterium-tuberculosis-lipids-to-induce-potent-cytokines-and-antibody-response-through-activation-of-%C3%AE-%C3%AE-t-cells-in-mice
#5
Ishani Das, Avinash Padhi, Sitabja Mukherjee, Debi Dash, Santosh Kar, Avinash Sonawane
Activation of cell mediated and humoral immune responses to Mycobacterium tuberculosis (Mtb) are critical for protection and that nanoparticles mediated delivery of antigens are more potent in inducing different immune responses. Herein, we show that mice immunized with Mtb lipid bound chitosan nanoparticles(NPs) induce secretion of prominent type 1 T helper (Th1) and type 2 T helper (Th2) cytokines in lymph node and spleen cells, and also induced significantly higher levels of IgG, IgG1, IgG2 and IgM in comparison to control mice...
February 16, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28203237/activation-of-the-wnt-pathway-by-mycobacterium-tuberculosis-a-wnt-wnt-situation
#6
REVIEW
Tomás Villaseñor, Edgardo Madrid-Paulino, Rafael Maldonado-Bravo, Antonio Urbán-Aragón, Leonor Pérez-Martínez, Gustavo Pedraza-Alva
Mycobacterium tuberculosis (M. tuberculosis), an intracellular pathogenic Gram-positive bacterium, is the cause of tuberculosis (TB), a major worldwide human infectious disease. The innate immune system is the first host defense against M. tuberculosis. The recognition of this pathogen is mediated by several classes of pattern recognition receptors expressed on the host innate immune cells, including Toll-like receptors, Nod-like receptors, and C-type lectin receptors like Dectin-1, the Mannose receptor, and DC-SIGN...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28201993/structure-and-variation-of-crispr-and-crispr-flanking-regions-in-deleted-direct-repeat-region-mycobacterium-tuberculosis-complex-strains
#7
Paul Jeffrey Freidlin, Israel Nissan, Anna Luria, Drora Goldblatt, Lana Schaffer, Hasia Kaidar-Shwartz, Daniel Chemtob, Zeev Dveyrin, Steven Robert Head, Efrat Rorman
BACKGROUND: CRISPR and CRISPR-flanking genomic regions are important for molecular epidemiology of Mycobacterium tuberculosis complex (MTBC) strains, and potentially for adaptive immunity to phage and plasmid DNA, and endogenous roles in the bacterium. Genotyping in the Israel National Mycobacterium Reference Center Tel-Aviv of over 1500 MTBC strains from 2008-2013 showed three strains with validated negative 43-spacer spoligotypes, that is, with putatively deleted direct repeat regions (deleted-DR/CRISPR regions)...
February 15, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28199374/a-novel-mycobacterial-in-vitro-infection-assay-identifies-differences-of-induced-macrophage-apoptosis-between-cd4-and-cd8-t-cells
#8
Vanesa Nkwouano, Sven Witkowski, Nidja Rehberg, Rainer Kalscheuer, Norman Nausch, Ertan Mayatepek, Marc Jacobsen
Macrophages are natural host cells for pathogenic mycobacteria, like Mycobacterium tuberculosis (M.tb). Immune surveillance by T cells and interaction with M.tb infected macrophages is crucial for protection against M.tb reactivation and development of active tuberculosis. Several factors play a role in the control of M.tb infection but reliable biomarkers remain elusive. One major obstacle is the absence of functional in vitro assays which allow concomitant determination of i) mycobacterial eradication; ii) cytotoxic effects on host macrophages; and iii) effector T-cell functions...
2017: PloS One
https://www.readbyqxmd.com/read/28196762/enteric-helminth-induced-type-i-interferon-signalling-protects-against-pulmonary-virus-infection-through-interaction-with-the-microbiota
#9
Amanda J McFarlane, Henry J McSorley, Donald J Davidson, Paul M Fitch, Claire Errington, Karen J Mackenzie, Eva S Gollwitzer, Chris J C Johnston, Andrew S MacDonald, Michael R Edwards, Nicola L Harris, Benjamin J Marsland, Rick M Maizels, Jürgen Schwarze
BACKGROUND: Helminth parasites have been reported to have beneficial immune modulatory effects in allergic and autoimmune conditions and detrimental consequences in tuberculosis and some viral infections. Their role in co-infection with respiratory viruses is not clear. OBJECTIVE: Here, we investigated the effects of strictly enteric helminth infection with Heligmosomoides polygyrus on respiratory syncytial virus (RSV) infection in a mouse model. METHODS: A murine helminth/ RSV co-infection model was developed...
February 11, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28194371/non-tuberculous-mycobacteria-in-south-african-wildlife-neglected-pathogens-and-potential-impediments-for-bovine-tuberculosis-diagnosis
#10
Nomakorinte Gcebe, Tiny M Hlokwe
Non-tuberculous mycobacteria (NTM) are not only emerging and opportunistic pathogens of both humans and animals, but from a veterinary point of view some species induce cross-reactive immune responses that hamper the diagnosis of bovine tuberculosis (bTB) in both livestock and wildlife. Little information is available about NTM species circulating in wildlife species of South Africa. In this study, we determined the diversity of NTM isolated from wildlife species from South Africa as well as Botswana. Thirty known NTM species and subspecies, as well as unidentified NTM, and NTM closely related to Mycobacterium goodii/Mycobacterium smegmatis were identified from 102 isolates cultured between the years 1998 and 2010, using a combination of molecular assays viz PCR and sequencing of different Mycobacterial house-keeping genes as well as single nucleotide polymorphism (SNP) analysis...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28193909/rv2299c-a-novel-dendritic-cell-activating-antigen-of-mycobacterium-tuberculosis-fused-esat-6-subunit-vaccine-confers-improved-and-durable-protection-against-the-hypervirulent-strain-hn878-in-mice
#11
Han-Gyu Choi, Seunga Choi, Yong Woo Back, Seungwha Paik, Hye-Soo Park, Woo Sik Kim, Hongmin Kim, Seung Bin Cha, Chul Hee Choi, Sung Jae Shin, Hwa-Jung Kim
Understanding functional interactions between DCs and antigens is necessary for achieving an optimal and desired immune response during vaccine development. Here, we identified and characterized protein Rv2299c (heat-shock protein 90 family), which effectively induced DC maturation. The Rv2299c-maturated DCs showed increased expression of surface molecules and production of proinflammatory cytokines. Rv2299c induced these effects by binding to TLR4 and stimulating the downstream MyD88-, MAPK- and NF-κB-dependent signaling pathways...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28193504/strong-anti-epstein-barr-virus-ebv-or-cytomegalovirus-cmv-cellular-immune-responses-predict-survival-and-a-favourable-response-to-anti-tuberculosis-therapy
#12
REVIEW
Tumaini Nagu, Said Aboud, Martin Rao, Mecky Matee, Rebecca Axelsson, Davide Valentini, Ferdinand Mugusi, Alimuddin Zumla, Markus Maeurer
BACKGROUND: Intact immune responses to cytomegalovirus (CMV) and Epstein-Barr virus (EBV) represent a biologically and clinically relevant correlate of 'immunological fitness' in humans. However, there is a lack of knowledge concerning anti-EBV or anti-CMV responses in patients with pulmonary tuberculosis (TB), in whom aberrant immune responses may promote progression of clinical disease. METHODS: Venous blood samples were obtained from at the time of (sputum smear positive) pulmonary TB diagnosis...
February 10, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28192579/infectious-diseases-and-immunizations-in-international-adoption
#13
Emily Obringer, Linda Walsh
Children who are adopted internationally have an increased risk of infectious diseases due to endemic conditions and variable access to preventive health care, such as vaccines, in their country of origin. Pediatricians and other providers who care for children should be familiar with the recommended screening for newly arrived international adoptees. Testing for gastrointestinal pathogens, tuberculosis, hepatitis, syphilis, and HIV should be routinely performed. Other endemic diseases and common skin infections may need to be assessed...
February 1, 2017: Pediatric Annals
https://www.readbyqxmd.com/read/28192437/species-dependent-impact-of-helminth-derived-antigens-on-human-macrophages-infected-with-mycobacterium-tuberculosis-direct-effect-on-the-innate-anti-mycobacterial-response
#14
Naomi Aira, Anna-Maria Andersson, Susmita K Singh, Derek M McKay, Robert Blomgran
BACKGROUND: In countries with a high prevalence of tuberculosis there is high coincident of helminth infections that might worsen disease outcome. While Mycobacterium tuberculosis (Mtb) gives rise to a pro-inflammatory Th1 response, a Th2 response is typical of helminth infections. A strong Th2 response has been associated with decreased protection against tuberculosis. PRINCIPAL FINDINGS: We investigated the direct effect of helminth-derived antigens on human macrophages, hypothesizing that helminths would render macrophages less capable of controlling Mtb...
February 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28192214/immune-recognition-surface-construction-of-mycobacterium-tuberculosis-epitope-specific-antibody-responses-in-tuberculosis-patients-identified-by-peptide-microarrays
#15
REVIEW
Davide Valentini, Martin Rao, Giovanni Ferrara, Marc Perkins, Ernest Dodoo, Alimuddin Zumla, Markus Maeurer
BACKGROUND: Understanding of humoral immune responses in tuberculosis (TB) is gaining interest, since B cells and antibodies may be important in diagnosis as well as protective immune responses. High-content peptide microarrays (HCPM) are highly precise and reliable for gauging specific antibody responses to pathogens, as well as autoantigens. METHODS: We used a HCPM comprising epitopes spanning 154 proteins of Mycobacterium tuberculosis (M. tb) to gauge specific IgG antibody responses in sera of TB patients from Africa and South America...
February 9, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28190740/protective-efficacy-of-a-lipid-antigen-vaccine-in-a-guinea-pig-model-of-tuberculosis
#16
Gérald Larrouy-Maumus, Emilie Layre, Simon Clark, Jacques Prandi, Emma Rayner, Marco Lepore, Gennaro de Libero, Ann Williams, Germain Puzo, Martine Gilleron
The bacillus Calmette Guérin (BCG) vaccine, the only licensed vaccine against TB, displays partial and variable efficacy, thus making the exploitation of novel vaccination strategies a major priority. Most of the current vaccines in pre-clinical or clinical development are based on the induction of T cells recognizing protein antigens. However, a large number of T cells specific for mycobacterial lipids are induced during infection, suggesting that lipid-based vaccines might represent an important component of novel sub-unit vaccines...
February 9, 2017: Vaccine
https://www.readbyqxmd.com/read/28188493/serious-fungal-infections-in-chile
#17
E Alvarez Duarte, D W Denning
The incidence and prevalence of fungal infections in Chile are unknown. Here, we have estimated the burden of serious fungal diseases from data obtained from clinical reports, WHO reports, Chilean census, OECD reports and comprehensive literature search available on PubMed and SciELO, among other scientific resources. Due the lack of official data about fungal diseases, frequencies were calculated based on the specific populations at risk. Recurrent vulvovaginal candidiasis (>4 episodes/year) is estimated to occur in 3108/100,000...
February 10, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28188492/serious-fungal-infections-in-portugal
#18
R Sabino, C Verissímo, J Brandão, C Martins, D Alves, C Pais, D W Denning
There is a lack of knowledge on the epidemiology of fungal infections worldwide because there are no reporting obligations. The aim of this study was to estimate the burden of fungal disease in Portugal as part of a global fungal burden project. Most published epidemiology papers reporting fungal infection rates from Portugal were identified. Where no data existed, specific populations at risk and fungal infection frequencies in those populations were used in order to estimate national incidence or prevalence, depending on the condition...
February 10, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28183185/rational-design-of-selective-and-bioactive-inhibitors-of-the-mycobacterium-tuberculosis-proteasome
#19
Kyle A Totaro, Dominik Barthelme, Peter T Simpson, Xiuju Jiang, Gang Lin, Carl F Nathan, Robert T Sauer, Jason K Sello
The 20S core particle of the proteasome in Mycobacterium tuberculosis (Mtb) is a promising, yet unconventional, drug target. This multimeric peptidase is not essential, yet degrades proteins that have become damaged and toxic via reactions with nitric oxide (and/or the associated reactive nitrogen intermediates) produced during the host immune response. Proteasome inhibitors could render Mtb susceptible to the immune system, but they would only be therapeutically viable if they do not inhibit the essential 20S counterpart in humans...
February 10, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28178208/effector-mechanisms-of-neutrophils-within-the-innate-immune-system-in-response-to-mycobacterium-tuberculosis-infection
#20
REVIEW
Eric Warren, Garrett Teskey, Vishwanath Venketaraman
Neutrophils have a significant yet controversial role in the innate immune response to Mycobacterium tuberculosis (M. tb) infection, which is not yet fully understood. In addition to neutrophils' well-known effector mechanisms, they may also help control infection of M. tb through the formation of neutrophil extracellular traps (NETs), which are thought to further promote the killing of M. tb by resident alveolar macrophages. Cytokines such as IFN-γ have now been shown to serve an immunomodulatory role in neutrophil functioning in conjunction to its pro-inflammatory function...
February 7, 2017: Journal of Clinical Medicine
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