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Tuberculosis and immune response

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https://www.readbyqxmd.com/read/27918526/mycobacterium-tuberculosis-esxh-inhibits-escrt-dependent-cd4-t-cell-activation
#1
Cynthia Portal-Celhay, JoAnn M Tufariello, Smita Srivastava, Aleena Zahra, Thais Klevorn, Patricia S Grace, Alka Mehra, Heidi S Park, Joel D Ernst, William R Jacobs, Jennifer A Philips
Mycobacterium tuberculosis (Mtb) establishes a persistent infection, despite inducing antigen-specific T-cell responses. Although T cells arrive at the site of infection, they do not provide sterilizing immunity. The molecular basis of how Mtb impairs T-cell function is not clear. Mtb has been reported to block major histocompatibility complex class II (MHC-II) antigen presentation; however, no bacterial effector or host-cell target mediating this effect has been identified. We recently found that Mtb EsxH, which is secreted by the Esx-3 type VII secretion system, directly inhibits the endosomal sorting complex required for transport (ESCRT) machinery...
December 5, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27914741/maternal-bcg-scar-is-associated-with-increased-infant-proinflammatory-immune-responses
#2
Patrice Akusa Mawa, Emily L Webb, Abdelali Filali-Mouhim, Gyaviira Nkurunungi, Rafick-Pierre Sekaly, Swaib Abubaker Lule, Sarah Prentice, Stephen Nash, Hazel M Dockrell, Alison M Elliott, Stephen Cose
INTRODUCTION: Prenatal exposures such as infections and immunisation may influence infant responses. We had an opportunity to undertake an analysis of innate responses in infants within the context of a study investigating the effects of maternal mycobacterial exposures and infection on BCG vaccine-induced responses in Ugandan infants. MATERIAL AND METHODS: Maternal and cord blood samples from 29 mother-infant pairs were stimulated with innate stimuli for 24h and cytokines and chemokines in supernatants were measured using the Luminex® assay...
November 30, 2016: Vaccine
https://www.readbyqxmd.com/read/27914454/-suppressor-factor-of-neutrophils-a-short-story-of-a-long-term-misconception
#3
I A Linge, E V Kondratieva, T K Kondratieva, V A Makarov, V I Polshakov, O Yu Savelyev, A S Apt
A large body of evidence obtained during the last decade has demonstrated that neutrophils suppress T cell proliferation in different models of inflammation and cell interaction. The commonly used method for assessing cell proliferation and proliferation inhibition is measuring [3H]thymidine incorporation into cells. Earlier, we observed inhibition of [3H]thymidine uptake in experiments on neutrophil-mediated regulation of T cell response in tuberculosis immunity. Here, we used different types of proliferating cells to analyze the nature of the soluble "neutrophil factor" by a variety of methods (dialysis, HPLC, mass spectrometry, and NMR) and unambiguously demonstrated that neutrophils do not synthesize a specific factor inhibiting cell proliferation, but secrete high concentrations of extracellular thymidine that competitively inhibit [3H]thymidine incorporation...
November 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27908271/host-directed-therapeutics-against-mycobacterial-infections
#4
Haruaki Tomioka, Chiaki Sano, Yutaka Tatano
The high incidence of tuberculosis (TB) in the world, especially in developing countries, the resurgence of TB in industrialized countries, and the global increase in the prevalence of Mycobacterium avium complex infections in immunocompromised hosts have prompted the quest for novel antimycobacterial drugs. However, the development of such antimicrobial chemotherapeutics is currently making very slow progress even with using the bioinformatics-based methodology for drug design. It thus appears that devising improved administration protocols for clinical treatment against intractable mycobacterial infections using existing chemotherapeutics is more practical than awaiting the development of new antimycobacterial drugs...
December 2, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27902779/differential-cytokine-gene-expression-in-granulomas-from-lungs-and-lymph-nodes-of-cattle-experimentally-infected-with-aerosolized-mycobacterium-bovis
#5
Mitchell V Palmer, Tyler C Thacker, W Ray Waters
The hallmark lesion of tuberculosis in humans and animals is the granuloma. The granuloma represents a distinct host cellular immune response composed of epithelioid macrophages, lymphocytes, and multinucleated giant cells, often surrounding a caseous necrotic core. Within the granuloma, host-pathogen interactions determine disease outcome. Factors within the granulomas such as cytokines and chemokines drive cell recruitment, activity, function and ultimately the success or failure of the host's ability to control infection...
2016: PloS One
https://www.readbyqxmd.com/read/27900465/polymorphisms-in-beta-2-adrenergic-receptor-gene-and-association-with-tuberculosis
#6
Abbas Farzin Azar, Nima Hosseini Jazani, Ahad Bazmani, Ali Vahhabi, Shahram Shahabi
PURPOSE: Genetic susceptibility for tuberculosis in human has been previously demonstrated. Polymorphisms in genes involved in immune responses may alter the susceptibility of individuals to tuberculosis. Polymorphisms of beta-2 adrenergic receptor (ADRB2) gene can be possibly an important risk factor in tuberculosis. In this study, the association between rs1042713 (Arg16Gly +46A>G) and rs1042714 (Gln27Glu +79C>G) polymorphisms in ADRB2 gene and tuberculosis was evaluated. METHODS: Genotype distributions of the rs1042713 (Arg16Gly +46A>G) and rs1042714 (Gln27Glu +79C>G) polymorphisms in ADRB2 gene in 106 patients with pulmonary tuberculosis and 88 healthy subjects were studied by PCR-RFLP method in an Iranian population...
November 29, 2016: Lung
https://www.readbyqxmd.com/read/27893795/virulence-of-mycobacterium-tuberculosis-after-acquisition-of-isoniazid-resistance-individual-nature-of-katg-mutants-and-the-possible-role-of-ahpc
#7
Luisa Maria Nieto R, Carolina Mehaffy, Elizabeth Creissen, JoLynn Troudt, Amber Troy, Helle Bielefeldt-Ohmann, Marcos Burgos, Angelo Izzo, Karen M Dobos
In the last decade, there were 10 million new tuberculosis cases per year globally. Around 9.5% of these cases were caused by isoniazid resistant (INHr) Mycobacterium tuberculosis (Mtb) strains. Although isoniazid resistance in Mtb is multigenic, mutations in the catalase-peroxidase (katG) gene predominate among the INHr strains. The effect of these drug-resistance-conferring mutations on Mtb fitness and virulence is variable. Here, we assessed differences in bacterial growth, immune response and pathology induced by Mtb strains harboring mutations at the N-terminus of the katG gene...
2016: PloS One
https://www.readbyqxmd.com/read/27892960/new-genome-wide-algorithm-identifies-novel-in-vivo-expressed-mycobacterium-tuberculosis-antigens-inducing-human-t-cell-responses-with-classical-and-unconventional-cytokine-profiles
#8
Mariateresa Coppola, Krista E van Meijgaarden, Kees L M C Franken, Susanna Commandeur, Gregory Dolganov, Igor Kramnik, Gary K Schoolnik, Inaki Comas, Ole Lund, Corine Prins, Susan J F van den Eeden, Gro E Korsvold, Fredrik Oftung, Annemieke Geluk, Tom H M Ottenhoff
New strategies are needed to develop better tools to control TB, including identification of novel antigens for vaccination. Such Mtb antigens must be expressed during Mtb infection in the major target organ, the lung, and must be capable of eliciting human immune responses. Using genome-wide transcriptomics of Mtb infected lungs we developed data sets and methods to identify IVE-TB (in-vivo expressed Mtb) antigens expressed in the lung. Quantitative expression analysis of 2,068 Mtb genes from the predicted first operons identified the most upregulated IVE-TB genes during in-vivo pulmonary infection...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27891500/interspecies-communication-between-pathogens-and-immune-cells-via-bacterial-membrane-vesicles
#9
Katerina S Jurkoshek, Ying Wang, Jaffre J Athman, Marian R Barton, Pamela A Wearsch
The production of extracellular vesicles is a universal mechanism for intercellular communication that is conserved across kingdoms. Prokaryotes secrete 50-250 nm membrane vesicles (MVs) in a manner that is regulated by environmental stress and is thought to promote survival. Since many types of host-derived stress are encountered during infection, this implies an important role for MV secretion in bacterial pathogenesis. Accordingly, MVs produced by gram-positive and gram-negative pathogens contain toxins, virulence factors, and other molecules that promote survival in the host...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27889398/recognition-of-mycobacterial-lipids-by-immune-receptors
#10
REVIEW
Eri Ishikawa, Daiki Mori, Sho Yamasaki
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), infects one-third of the world's population and causes 1.5 million deaths each year. The cell envelopes of mycobacteria comprise a wealth of unique glycolipids, including trehalose-6,6'-dimycolate (TDM), lipoarabinomannan (LAM), lipomannan (LM), and phosphatidylinositol (PI) mannosides (PIMs). These lipids are important modulators of the host immune responses during infection and in some cases have been used as adjuvants [e.g., complete Freund's adjuvant (CFA)]...
November 23, 2016: Trends in Immunology
https://www.readbyqxmd.com/read/27883091/mycobacterium-tuberculosis-triggered-hippo-pathway-orchestrates-cxcl1-2-expression-to-modulate-host-immune-responses
#11
Monoranjan Boro, Vikas Singh, Kithiganahalli Narayanaswamy Balaji
Mycobacterium tuberculosis (Mtb) pathogenesis encompasses a plethora of finely regulated alterations within the host which eventually coin the outcome of infection. Chemokines are important components in directing immune cell recruitment to the site of infection, and shaping the disease progression. Here, we demonstrate that Hippo (mammalian sterile 20-like 1 and 2 kinases, MST1/2, in mammals), is activated during mycobacterial infection in a toll-like receptor (TLR) 2-interleukin receptor-1 associated kinases (IRAK1/4)-dependent manner...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27879332/mucosal-bcg-vaccination-induces-protective-lung-resident-memory-t-cell-populations-against-tuberculosis
#12
Carolina Perdomo, Ulrike Zedler, Anja A Kühl, Laura Lozza, Philippe Saikali, Leif E Sander, Alexis Vogelzang, Stefan H E Kaufmann, Andreas Kupz
: Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB), yet its moderate efficacy against pulmonary TB calls for improved vaccination strategies. Mucosal BCG vaccination generates superior protection against TB in animal models; however, the mechanisms of protection remain elusive. Tissue-resident memory T (TRM) cells have been implicated in protective immune responses against viral infections, but the role of TRM cells following mycobacterial infection is unknown...
November 22, 2016: MBio
https://www.readbyqxmd.com/read/27867751/t7-phage-display-library-a-promising-strategy-to-detect-tuberculosis-specific-biomarkers
#13
Harvinder Talwar, Jaya Talreja, Lobelia Samavati
One-third of the world's population is infected with tuberculosis, only 10% will develop active disease and the remaining 90% is considered to have latent TB (LTB). While active TB is contagious and can be lethal, the LTB can evolve to active TB. The diagnosis of TB can be challenging, especially in the early stages, due to the variability in presentation and nonspecific signs and symptoms. Currently, we have limited tools available to diagnose active TB, predict treatment efficacy and cure of active tuberculosis, the reactivation of latent tuberculosis infection, and the induction of protective immune responses through vaccination...
June 2016: Mycobacterial Diseases: Tuberculosis & Leprosy
https://www.readbyqxmd.com/read/27867196/extracellular-adp-facilitates-monocyte-recruitment-in-bacterial-infection-via-erk-signaling
#14
Xiaoyu Zhang, Juliang Qin, Junyan Zou, Zhangsheng Lv, Binghe Tan, Jueping Shi, Yihan Zhao, Hua Ren, Mingyao Liu, Min Qian, Bing Du
As the most prominent clinical drug targets for the inhibition of platelet aggregation, P2Y12 and P2Y13 have been found to be highly expressed in both platelets and macrophages. However, the roles and function of P2Y12/13 in the regulation of macrophage-mediated innate immune responses remain unclear. Here, we demonstrate that adenosine 5'-diphosphate (ADP), the endogenous ligand of P2Y1, P2Y12 and P2Y13, was released both in E. coli-infected mice and from macrophages treated with either lipopolysaccharide (LPS) or Pam3CSK4...
November 21, 2016: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/27866772/h1-ic31-vaccination-is-safe-and-induces-long-lived-tnf-%C3%AE-il-2-cd4-t-cell-responses-in-m-tuberculosis-infected-and-uninfected-adolescents-a-randomized-trial
#15
Helen Mearns, Hennie D Geldenhuys, Benjamin M Kagina, Munyaradzi Musvosvi, Francesca Little, Frances Ratangee, Hassan Mahomed, Willem A Hanekom, Søren T Hoff, Morten Ruhwald, Ingrid Kromann, Peter Bang, Mark Hatherill, Peter Andersen, Thomas J Scriba
BACKGROUND: Control of the tuberculosis epidemic requires a novel vaccine that is effective in preventing tuberculosis in adolescents, a key target population for vaccination against TB. METHODS: Healthy adolescents, stratified by M. tuberculosis-infection status, were enrolled into this observer-blinded phase II clinical trial of the protein-subunit vaccine candidate, H1:IC31, comprising a fusion protein (H1) of Ag85B and ESAT-6, formulated with the IC31 adjuvant...
November 17, 2016: Vaccine
https://www.readbyqxmd.com/read/27866220/molecular-basis-of-mycobacterial-survival-in-macrophages
#16
REVIEW
Jane Atesoh Awuh, Trude Helen Flo
Macrophages play an essential role in the immune system by ingesting and degrading invading pathogens, initiating an inflammatory response and instructing adaptive immune cells, and resolving inflammation to restore homeostasis. More interesting is the fact that some bacteria have evolved to use macrophages as a natural habitat and tools of spread in the host, e.g., Mycobacterium tuberculosis (Mtb) and some non-tuberculous mycobacteria (NTM). Mtb is considered one of humanity's most successful pathogens and is the causal agent of tuberculosis, while NTMs cause opportunistic infections all of which are of significant public health concern...
November 19, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27865396/mycobacterium-smegmatis-proteoliposome-induce-protection-in-a-murine-progressive-pulmonary-tuberculosis-model
#17
Yanely Tirado, Alina Puig, Nadine Alvarez, Reinier Borrero, Alicia Aguilar, Frank Camacho, Fatima Reyes, Sonsire Fernandez, Jose Luis Perez, Reynaldo Acevedo, Dulce Mata Espinoza, Jorge Alberto Barrios Payan, Maria de Los A Garcia, Ramlah Kadir, María E Sarmiento, Rogelio Hernandez-Pando, Mohd-Nor Norazmi, Armando Acosta
Tuberculosis (TB) remains an important cause of mortality and morbidity. The TB vaccine, BCG, is not fully protective against the adult form of the disease and is unable to prevent its transmission although it is still useful against severe childhood TB. Hence, the search for new vaccines is of great interest. In a previous study, we have shown that proteoliposomes obtained from Mycobacterium smegmatis (PLMs) induced cross reactive humoral and cellular response against Mycobacterium tuberculosis (Mtb) antigens...
December 2016: Tuberculosis
https://www.readbyqxmd.com/read/27865394/recent-developments-in-genomics-bioinformatics-and-drug-discovery-to-combat-emerging-drug-resistant-tuberculosis
#18
REVIEW
Soumya Swaminathan, Jagadish Chandrabose Sundaramurthi, Alangudi Natarajan Palaniappan, Sujatha Narayanan
Emergence of drug-resistant tuberculosis (DR-TB) is a big challenge in TB control. The delay in diagnosis of DR-TB leads to its increased transmission, and therefore prevalence. Recent developments in genomics have enabled whole genome sequencing (WGS) of Mycobacterium tuberculosis (M. tuberculosis) from 3-day-old liquid culture and directly from uncultured sputa, while new bioinformatics tools facilitate to determine DR mutations rapidly from the resulting sequences. The present drug discovery and development pipeline is filled with candidate drugs which have shown efficacy against DR-TB...
December 2016: Tuberculosis
https://www.readbyqxmd.com/read/27865392/mycobacterium-indicus-pranii-mip-mediated-host-protective-intracellular-mechanisms-against-tuberculosis-infection-involvement-of-tlr-4-mediated-signaling
#19
Shibali Das, Bidisha Paul Chowdhury, Avranil Goswami, Shabina Parveen, Junaid Jawed, Nishith Pal, Subrata Majumdar
Mycobacterium tuberculosis infection inflicts the disease Tuberculosis (TB), which is fatal if left untreated. During M. tuberculosis infection, the pathogen modulates TLR-4 receptor down-stream signaling, indicating the possible involvement of TLR-4 in the regulation of the host immune response. Mycobacterium indicus pranii (MIP) possesses immuno-modulatory properties which induces the pro-inflammatory responses via induction of TLR-4-mediated signaling. Here, we observed the immunomodulatory properties of MIP against tuberculosis infection...
December 2016: Tuberculosis
https://www.readbyqxmd.com/read/27865389/mycobacterium-indicus-pranii-as-a-booster-vaccine-enhances-bcg-induced-immunity-and-confers-higher-protection-in-animal-models-of-tuberculosis
#20
Mohd Saqib, Rahul Khatri, Bindu Singh, Ananya Gupta, Arvind Kumar, Sangeeta Bhaskar
BCG, the only approved vaccine protects against severe form of childhood tuberculosis but its protective efficacy wanes in adolescence. BCG has reduced the incidence of infant TB considerably in endemic areas; therefore prime-boost strategy is the most realistic measure for control of tuberculosis in near future. Mycobacterium indicus pranii (MIP) shares significant antigenic repertoire with Mtb and BCG and has been shown to impart significant protection in animal models of tuberculosis. In this study, MIP was given as a booster to BCG vaccine which enhanced the BCG mediated immune response, resulting in higher protection...
December 2016: Tuberculosis
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