Read by QxMD icon Read

Pathogenesis AND Tuberculosis

Suzaan Marais, Rachel P J Lai, Katalin A Wilkinson, Graeme Meintjes, Anne O'Garra, Robert J Wilkinson
Tuberculosis meningitis (TBM) is a frequent cause of meningitis in HIV-infected individuals, resulting in death in ~ 40% of affected patients. A severe complication of antiretroviral therapy (ART) in these patients is neurological TB-immune reconstitution inflammatory syndrome (IRIS), but its underlying cause remains poorly understood. To investigate the pathogenesis of TBM-IRIS, we performed longitudinal whole blood microarray analysis of HIV-infected TBM patients and reflected the findings at the protein level...
December 8, 2016: Journal of Infectious Diseases
Ashley L Garner, Jayan Rammohan, Jeremy P Huynh, Lucas M Onder, James Chen, Brian Bae, Drake Jensen, Leslie A Weiss, Ana Ruiz Manzano, Seth A Darst, Elizabeth A Campbell, Bryce E Nickels, Eric A Galburt, Christina L Stallings
: CarD is an essential RNA polymerase (RNAP) interacting protein in Mycobacterium tuberculosis (Mtb) that stimulates formation of RNAP-promoter open complexes. CarD plays a complex role in Mtb growth and virulence that is not fully understood. Therefore, to gain further insight into the role of CarD in Mtb growth and virulence we determined the effect of increasing the affinity of CarD for RNAP. Using site-directed mutagenesis guided by crystal structures of CarD bound to RNAP, we identified amino acid substitutions that increase the affinity of CarD for RNAP...
December 5, 2016: Journal of Bacteriology
Julia Lienard, Fredric Carlsson
Mycobacteria are a major human health problem globally. Regarding tuberculosis the situation is worsened by the poor efficacy of current vaccine regimens and by emergence of drug-resistant strains (Manjelievskaia J et al, Trans R Soc Trop Med Hyg 110: 110, 2016; Pereira et al., Lancet Infect Dis 12:300-306, 2012; undermining both disease-prevention and available treatments. Thus, increased basic understanding of mycobacterial-and particularly Mycobacterium tuberculosis-virulence strategies and pathogenesis is of great importance...
2017: Methods in Molecular Biology
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
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
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
C Seshadri, N T T Thuong, N T H Mai, N D Bang, T T H Chau, D M Lewinsohn, G E Thwaites, S J Dunstan, T R Hawn
The MR1 antigen-presenting system is conserved among mammals and enables T cells to recognize small molecules produced by bacterial pathogens, including Mycobacterium tuberculosis (M.tb). However, it is not known whether MR1-mediated antigen presentation is important for protective immunity against mycobacterial disease. We hypothesized that genetic control of MR1 expression correlates with clinical outcomes of tuberculosis infection. We performed an MR1 candidate gene association study and identified an intronic single-nucleotide polymorphism (rs1052632) that was significantly associated with susceptibility to tuberculosis in a discovery and validation cohort of Vietnamese adults with tuberculosis...
November 24, 2016: Genes and Immunity
Monu, Laxman S Meena
OBJECTIVES: The periodic binding of protein expressed by Mycobacterium tuberculosis H37Rv with the host cell receptor molecules i.e. fibronectin (Fn) is gaining significance because of its adhesive properties. The genome sequencing of M. tuberculosis H37Rv revealed that the proline-glutamic (PE) proteins contain polymorphic GC-rich repetitive sequences (PGRS) which have clinical importance in pathogenesis events when the host encounters M. tuberculosis H37Rv. The functional parts of PE_PGRS family proteins, have not been extensively studied in tuberculosis biology...
October 2016: Iranian Journal of Basic Medical Sciences
Lei Shen, Hong Shi, Yan Gao, Qinfang Ou, Qianqian Liu, Yuanyuan Liu, Jing Wu, Wenhong Zhang, Lin Fan, Lingyun Shao
PD-1 is a cell surface receptor of activated T and B lymphocytes and it's role in tuberculosis is controversial because of lack of congruence between clinical study and animal model. To investigate the immunological pathogenesis mechanisms of tuberculosis and to develop the immune therapy target essential for controlling tuberculosis, here we explored the expression characteristics and dynamic changes of PD-1/PD-L1 pathway in different CD4+T cell subsets. We enrolled 24 human subjects including 15 active tuberculosis (ATB) patients and 9 healthy donors (HD)...
December 2016: Tuberculosis
M Doerflinger, W Forsyth, G Ebert, M Pellegrini, M J Herold
Infectious diseases are a leading cause of death worldwide. Novel therapeutics are urgently required to treat multidrug-resistant organisms such as Mycobacterium tuberculosis and to mitigate morbidity and mortality caused by acute infections such as malaria and dengue fever virus as well as chronic infections such as human immunodeficiency virus-1 and hepatitis B virus. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, which has revolutionized biomedical research, holds great promise for the identification and validation of novel drug targets...
November 16, 2016: Cellular Microbiology
Lúcia Moreira-Teixeira, Jeremy Sousa, Finlay W McNab, Egídio Torrado, Filipa Cardoso, Henrique Machado, Flávia Castro, Vânia Cardoso, Joana Gaifem, Xuemei Wu, Rui Appelberg, António Gil Castro, Anne O'Garra, Margarida Saraiva
Tuberculosis causes ∼1.5 million deaths every year, thus remaining a leading cause of death from infectious diseases in the world. A growing body of evidence demonstrates that type I IFN plays a detrimental role in tuberculosis pathogenesis, likely by interfering with IFN-γ-dependent immunity. In this article, we reveal a novel mechanism by which type I IFN may confer protection against Mycobacterium tuberculosis infection in the absence of IFN-γ signaling. We show that production of type I IFN by M. tuberculosis-infected macrophages induced NO synthase 2 and inhibited arginase 1 gene expression...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Hlumani Ndlovu, Mohlopheni J Marakalala
Tuberculosis (TB) remains a leading global health problem that is aggravated by emergence of drug-resistant strains, which account for increasing number of treatment-refractory cases. Thus, eradication of this disease will strongly require better therapeutic strategies. Identification of host factors promoting disease progression may accelerate discovery of adjunct host-directed therapies (HDTs) that will boost current treatment protocols. HDTs focus on potentiating key components of host anti-mycobacterial effector mechanisms, and limiting inflammation and pathological damage in the lung...
2016: Frontiers in Immunology
Marcus Ang, Soon-Phaik Chee
Ocular tuberculosis still remains a presumptive, clinical diagnosis in the presence of supportive clinical signs and investigations, while in the absence of other possible causes of uveitis. The purpose of this review is to discuss three controversies of ocular tuberculosis today. First, it is unclear from many reports on how the diagnosis of ocular tuberculosis was defined, and if they included 'probable' or 'possible' diagnoses. Thus, there is a need to standardise the terminology used for ocular tuberculosis to allow for comparisons among studies...
November 4, 2016: British Journal of Ophthalmology
Anthony Ca Yii, Mariko S Koh, Therese S Lapperre, Gan L Tan, Sanjay H Chotirmall
Chronic lung disease is recognized as an important risk factor for developing pulmonary aspergillosis. The development of specific aspergillus-associated syndromes depends on host immunity and underlying lung disease. In the setting of asthma, hypersensitivity to Aspergillus can lead to allergic bronchopulmonary aspergillosis (ABPA) or severe asthma with fungal sensitization (SAFS). Chronic use of systemic or inhaled corticosteroids coupled with recurrent antibiotic use for exacerbations prevalent in chronic obstructive pulmonary disease (COPD) predisposes to chronic pulmonary aspergillosis (CPA)...
January 1, 2017: Frontiers in Bioscience (Scholar Edition)
L A Semenova, S G Radenska-Lopovok, S A Burtseva, Yu S Berezovsky, L N Lepekha
Necrotizing sarcoid granulomatosis (NSG) belongs to productive small-vessel vasculitis with the formation of sarcoid-like granulomas, which is accompanied by ischemic necrosis of varying degrees and duration. The disease involves the lung only. The clinical symptoms of the disease are nonspecific so the latter is detected rather rarely. The main diagnostic technique is morphological examination. Immune complex inflammation develops in the vessel walls with the formation of macrophage-histiocytic granulomas that do not contain epithelioid cells...
2016: Arkhiv Patologii
Le Guo, Jin Zhao, Yuliang Qu, Runting Yin, Qian Gao, Shuqin Ding, Ying Zhang, Jun Wei, Guangxian Xu
Autophagy plays important roles in the host immune response against mycobacterial infection. Mycobacterium tuberculosis (M. tuberculosis) can live in macrophages owing to its ability to evade attacks by regulating autophagic response. MicroRNAs (miRNAs) are small noncoding, endogenously encoded RNA which plays critical roles in precise regulation of macrophage functions. Whether miRNAs specifically influence the activation of macrophage autophagy during M. tuberculosis infection are largely unknown. In this study, we demonstrate that BCG infection of macrophages resulted in enhanced expression of miRNA-20a, which inhibits autophagic process by targeting ATG7 and ATG16L1 and promotes BCG survival in macrophages...
2016: Frontiers in Cellular and Infection Microbiology
Toru Usui, Xiaoli Meng, Katy Saide, John Farrell, Paul Thomson, Paul Whitaker, John Watson, Neil S French, B Kevin Park, Dean J Naisbitt
Isoniazid, rifampicin, pyrazinamide and ethambutol are commonly used for the treatment of tuberculosis. Drug exposure is occasionally associated with liver and/or skin injury. The aim of this study was to determine whether drug-specific T-cells are detectable in patients with adverse reactions and if so characterize the nature of the T-cell response. PBMC from 6 patients with anti-tuberculosis drug-related adverse reactions (4 liver, 2 skin) were used to detect drug-responsive T-lymphocytes. Positive lymphocyte transformation test and/or ELIspot results were observed with all 6 patients...
November 1, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Kirsten E Wiens, Joel D Ernst
Type I interferons (IFNs, including IFN-αβ) contribute to the pathogenesis of Mycobacterium tuberculosis strains that induce high IFN-αβ levels. In the current study we examined the role of IFN-αβ during infection with a Mycobacterium africanum strain that induces low IFN-β levels. We infected wild-type and IFN-αβ receptor knockout mice with M. africanum and monitored bacterial growth, lung disease, and survival over 292 days. We found reduced lung bacterial burdens and less severe histopathological findings in the absence of IFN-αβ signaling...
December 15, 2016: Journal of Infectious Diseases
Ryan Jay Ohr, Mark Anderson, Miaomiao Shi, Olaf Schneewind, Dominique Missiakas
: Specialized secretion systems of bacteria evolved for selective advantage, either killing microbial competitors or implementing effector functions during parasitism. Earlier work characterized the ESAT-6 Secretion System (ESS) of Staphylococcus aureus and demonstrated its contribution to staphylococcal persistent infection of vertebrate hosts. Here we identify a novel secreted effector of the ESS pathway, EssD, that functions as a nuclease and cleaves DNA, but not RNA. EssI, a protein of the DUF600 family, binds EssD to block its nuclease activity in the staphylococcal cytoplasm...
October 17, 2016: Journal of Bacteriology
Vivek Naranbhai
Familial risk of tuberculosis (TB) has been recognized for centuries. Largely through studies of mono- and dizygotic twin concordance rates, studies of families with Mendelian susceptibility to mycobacterial disease, and candidate gene studies performed in the 20th century, it was recognized that susceptibility to TB disease has a substantial host genetic component. Limitations in candidate gene studies and early linkage studies made the robust identification of specific loci associated with disease challenging, and few loci have been convincingly associated across multiple populations...
October 2016: Microbiology Spectrum
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"