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Pathogenesis AND Tuberculosis

Gareth Prosser, Julius Brandenburg, Norbert Reiling, Clifton Earl Barry, Robert J Wilkinson, Katalin A Wilkinson
M. tuberculosis is a facultative anaerobe and its characteristic pathological hallmark, the granuloma, exhibits hypoxia in humans and in most experimental models. Thus the host and bacillary adaptation to hypoxia is of central importance in understanding pathogenesis and thereby to derive new drug treatments and vaccines.
October 22, 2016: Microbes and Infection
Felix S Dube, Mamadou Kaba, F J Lourens Robberts, Lemese Ah Tow, Sugnet Lubbe, Heather J Zar, Mark P Nicol
BACKGROUND: Lower respiratory tract infection in children is increasingly thought to be polymicrobial in origin. Children with symptoms suggestive of pulmonary tuberculosis (PTB) may have tuberculosis, other respiratory tract infections or co-infection with Mycobacterium tuberculosis and other pathogens. We aimed to identify the presence of potential respiratory pathogens in nasopharyngeal (NP) samples from children with suspected PTB. METHOD: NP samples collected from consecutive children presenting with suspected PTB at Red Cross Children's Hospital (Cape Town, South Africa) were tested by multiplex real-time RT-PCR...
October 24, 2016: BMC Infectious Diseases
Paul Elkington, Marc Tebruegge, Salah Mansour
Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and provided original proof that an infectious agent can cause human disease. However, key steps in TB pathogenesis remain poorly understood. We propose that autoimmunity is a critical and overlooked process driving pathology in TB, and present clinical and experimental observations supporting this hypothesis.
October 19, 2016: Trends in Immunology
Madhukar Pai, Marcel Behr
The identification of individuals with latent tuberculosis infection (LTBI) is useful for both fundamental understanding of the pathogenesis of disease and for clinical and public health interventions (i.e., to prevent progression to disease). Basic research suggests there is a pathogenetic continuum from exposure to infection to disease, and individuals may advance or reverse positions within the spectrum, depending on changes in the host immunity. Unfortunately, there is no diagnostic test that resolves the various stages within the spectrum of Mycobacterium tuberculosis infection...
October 2016: Microbiology Spectrum
Racquel Domingo-Gonzalez, Oliver Prince, Andrea Cooper, Shabaana A Khader
Chemokines and cytokines are critical for initiating and coordinating the organized and sequential recruitment and activation of cells into Mycobacterium tuberculosis-infected lungs. Correct mononuclear cellular recruitment and localization are essential to ensure control of bacterial growth without the development of diffuse and damaging granulocytic inflammation. An important block to our understanding of TB pathogenesis lies in dissecting the critical aspects of the cytokine/chemokine interplay in light of the conditional role these molecules play throughout infection and disease development...
October 2016: Microbiology Spectrum
Fatemeh Nooshabadi, Hee-Jeong Yang, Yunfeng Cheng, Madeleine S Durkee, Hexin Xie, Jianghong Rao, Jeffrey D Cirillo, Kristen C Maitland
Tuberculosis is a pulmonary disease with an especially high mortality rate in immuno-compromised populations, specifically children and HIV positive individuals. The causative agent, Mycobacterium tuberculosis (Mtb), is a very slow growing and difficult organism to work with, making both diagnosis and development of effective treatments cumbersome. We utilize a fiber-optic fluorescence microendoscope integrated with a whole-body imaging system for in vivo Mtb detection. The system exploits an endogenous enzyme of Mtb (β-lactamase, or BlaC) using a BlaC-specific NIR fluorogenic substrate...
October 18, 2016: Journal of Biophotonics
Fatemeh Heidarnezhad, Amir Asnaashari, Seyed Abdolrahim Rezaee, Roghayeh Ghezelsofla, Kiarash Ghazvini, Narges Valizadeh, Reza Basiri, Aghigh Ziaeemehr, Somayeh Sobhani, Houshang Rafatpanah
OBJECTIVES: Tuberculosis is one of the most important infectious diseases with high mortality rates worldwide, especially in developing countries. Interleukin17 (IL-17) is an important acquired immunity cytokine, which is mainly produced by CD4(+)TH17 cells. It can recruit neutrophils and macrophages to the infected site in the lungs. IL-23 is one of the most important inducers of IL-17. In the present study, the expressions of IL-23 and IL-17 were examined in the pathogenesis of tuberculosis...
August 2016: Iranian Journal of Basic Medical Sciences
Susmita K Singh, Anna-Maria Andersson, Rada Ellegård, Cecilia S Lindestam Arlehamn, Alessandro Sette, Marie Larsson, Olle Stendahl, Robert Blomgran
HIV coinfection is the most prominent risk factor for progression of Mycobacterium tuberculosis (Mtb) infection into active tuberculosis (TB) disease. The mechanisms behind the increased transition from latent to active TB in coinfected individuals have not been well elucidated at the cellular level. We hypothesized that HIV infection contributes to Mtb pathogenesis by interfering with the dendritic cell (DC)-mediated immune control. Mtb-antigen processing and presentation are key events in the immune response against TB...
October 13, 2016: American Journal of Pathology
Christian S Lentz, Alvaro A Ordonez, Paulina Kasperkiewicz, Florencia La Greca, Anthony J O'Donoghue, Christopher J Schulze, James C Powers, Charles S Craik, Marcin Drag, Sanjay K Jain, Matthew Bogyo
Although serine proteases are important mediators of Mycobacterium tuberculosis (Mtb) virulence, there are currently no tools to selectively block or visualize members of this family of enzymes. Selective reporter substrates or activity-based probes (ABPs) could provide a means to monitor infection and response to therapy using imaging methods. Here, we use a combination of substrate selectivity profiling and focused screening to identify optimized reporter substrates and ABPs for the Mtb "Hydrolase important for pathogenesis 1" (Hip1) serine protease...
July 15, 2016: ACS Infectious Diseases
Pere-Joan Cardona
A major problem with tuberculosis (TB) control is the long duration of drug therapy-both for latent and for active TB. Therapeutic vaccination has been postulated to improve this situation, and to this end there are several candidates already in clinical phases of development. These candidates follow two main designs, namely bacilli-directed therapy based on inactivated -whole or -fragmented bacillus (Mycobacterium w and RUTI) or fusion proteins that integrate non-replicating bacilli -related antigens (H56 vaccine), and host-directed therapy to reduce the tissue destruction...
2016: Frontiers in Microbiology
Juliet C Peña, Wen-Zhe Ho
Among the animal models of tuberculosis (TB), the non-human primates, particularly rhesus macaques (Macaca fascicularis) and cynomolgus macaques (Macaca mulatta), share the greatest anatomical and physiological similarities with humans. Macaques are highly susceptible to Mycobacterium tuberculosis infection and manifest the complete spectrum of clinical and pathological manifestations of TB as seen in humans. Therefore, the macaque models have been used extensively for investigating the pathogenesis of M. tuberculosis infection and for preclinical testing of drugs and vaccines against TB...
August 2016: Microbiology Spectrum
Aniruddha Agarwal, Sarakshi Mahajan, Moncef Khairallah, Padmamalini Mahendradas, Amod Gupta, Vishali Gupta
Intraocular tuberculosis presents a diagnostic challenge because of its protean clinical manifestations. Thus, it becomes imperative to distinguish chorioretinal inflammation due to tuberculosis from other infectious as well as non-infectious posterior uveitis since the clinical manifestations of these entities may be quite similar. With advancing technology, a number of novel imaging modalities are available today that enable in vivo near-histologic assessment of the chorioretinal tissue, greatly aiding the clinician in establishing a diagnosis and monitoring the therapeutic response of tubercular lesions...
October 11, 2016: Ocular Immunology and Inflammation
Veena C Yeruva, Mamata Savanagouder, Radhika Khandelwal, Apoorva Kulkarni, Yogendra Sharma, Tirumalai R Raghunand
The hallmark feature of Mycobacterium tuberculosis (M.tb) the causative agent of human tuberculosis, is its complex lipid rich cell wall comprised primarily of mycolic acids, long chain fatty acids that play a key role in structural stability and permeability of the cell wall. In addition, they are involved in inhibiting phagosome-lysosome fusion and aid in granuloma formation during the pathogenic process. M.tb DesA1 is an essential acyl-acyl carrier protein desaturase predicted to catalyze the introduction of position specific double bonds during the biosynthesis of mycolic acids...
October 6, 2016: Biochemical and Biophysical Research Communications
Piotr Buda, Ryszard Grenda, Anna Wieteska-Klimczak, Piotr Gietka, Lidia Skobejko-Włodarska, Karina Felberg, Janusz Książyk
Eosinophilic cystitis (EC) is a rare inflammatory disorder of the urinary tract characterized by infiltration of bladder with eosinophils. The cause remains unclear, immunological mechanisms have been implicated in pathogenesis. Potential etiological factors include: tumors, allergy, parasitic infections, trauma. The disease may have a variable course, from a mild self-limiting, through common symptoms like: dysuria, hematuria, abdominal pain, tumor, to severe renal failure, with eosinophilic infiltration of the other organs and systemic complications...
2016: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Ji-Young Joo, Gil Sun Cha, Jin Chung, Ju-Youn Lee, Sung-Jo Kim, Jeomil Choi
BACKGROUND: Although periodontal pathogens show a strong association with the development of atherosclerosis, little is known about how a microorganism contributes to disease onset and progression. Oxidation of low-density lipoprotein (LDL) is a major risk factor of atherogenesis. The principal objective of our study was to evaluate the ability of peptide 19 (Pep19) of Porphyromonas gingivalis (P. gingivalis) heat shock protein (HSP) as a potent inducer of LDL oxidation, and as a secondary objective, to compare this ability with that of Pep19 from different bacteria...
October 7, 2016: Journal of Periodontology
Han-Gyu Choi, Seunga Choi, Yong Woo Back, Hye-Soo Park, Hyun Shik Bae, Chul Hee Choi, Hwa-Jung Kim
Macrophages constitute the first line of defense against Mycobacterium tuberculosis and are critical in linking innate and adaptive immunity. Therefore, the identification and characterization of mycobacterial proteins that modulate macrophage function are essential for understanding tuberculosis pathogenesis. In this study, we identified the novel macrophage-activating protein, Rv2882c, from M. tuberculosis culture filtrate proteins. Recombinant Rv2882c protein activated macrophages to secrete pro-inflammatory cytokines and express co-stimulatory and major histocompatibility complex molecules via Toll-like receptor 4, myeloid differentiation primary response protein 88, and Toll/IL-1 receptor-domain-containing adaptor inducing IFN-beta...
2016: PloS One
Pawan Kumar
The intricate relationship between tuberculosis (TB) and immune system remains poorly understood. It is generally believed that weakening of the immune response against Mycobacterium tuberculosis leads to reactivation of latent infection into the active pulmonary disease. However, heterogeneous nature of TB and failure of rationally designed vaccines in clinical trials raises serious questions against the simplistic view of TB as an outcome of weakened immunity. In the wake of accumulating human TB data, it is argued here that a hyperactive antimycobacterial immune response is to blame for the pathogenesis of pulmonary TB in immunocompetent adults...
December 2016: Clinical and Translational Medicine
J Shi, B H Sun, L R Zhou, X S Wang
Mycobacterium tuberculosis (Mtb) is known to be responsible for tuberculosis (TB), but the pathogenesis of this disease and the host defense mechanisms involved are, for the most part, poorly understood. In this study, we divided 30 male C57BL/6 mice into control and infection groups, and following injection with physiological saline or Mtb, respectively, euthanized five mice from each group on days 1, 3, and 7. TNF-α and IL-10 levels were measured by enzyme-linked immunosorbent assay and flow cytometry, with the latter also being performed to assess apoptosis rates...
September 23, 2016: Genetics and Molecular Research: GMR
Abualgasim Elgaili Abdalla, Xiangke Duan, Wanyan Deng, Jie Zeng, Jianping Xie
Macrophages are crucial player in the defense against multiple intracellular pathogens. Mycobacterium tuberculosis, the causative agent of tuberculosis which inflicted around one third of global population, can replicate and persist within macrophages. MicroRNAs, endogenous, small noncoding RNA, can regulate the expression of macrophages genes required for appropriate signaling. Mycobacteria can manipulate the expression of macrophages microRNAs to subvert cell response for its survival and persistence. This review summarized the progress of microRNAs in mycobacterial pathogenesis...
September 28, 2016: Infection, Genetics and Evolution
Seow Hoon Saw, Joon Liang Tan, Xin Yue Chan, Kok Gan Chan, Yun Fong Ngeow
BACKGROUND: Meningitis is a major cause of mortality in tuberculosis (TB). It is not clear what factors promote central nervous system invasion and pathology but it has been reported that certain strains of Mycobacterium tuberculosis (Mtb) might have genetic traits associated with neurotropism. METHODS: In this study, we generated whole genome sequences of eight clinical strains of Mtb that were isolated from the cerebrospinal fluid (CSF) of patients presenting with tuberculous meningitis (TBM) in Malaysia, and compared them to the genomes of H37Rv and other respiratory Mtb genomes either downloaded from public databases or extracted from local sputum isolates...
2016: PeerJ
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