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Tuberculosis and immune response

Kartik Ramakrishna, Kalpana Premkumar, Jayakanthan Kabeerdoss, K R John
BACKGROUND & AIM: Innate immune responses are important in susceptibility to pulmonary tuberculosis (TB). In order to test the hypothesis that Toll-like receptor (TLR) 2 function would be abnormal in patients with active pulmonary TB we compared the cytokine responses of peripheral blood mononuclear cells (PBMC) to innate immune ligands in a case-control study. METHODS: PBMC from 19 untreated pulmonary TB patients, 17 healthy controls, and 11 treated pulmonary TB patients, were cultured for 24h with TLR 2 ligand (PAM-CSK) and other TLR ligands (muramyl dipeptide, flagellin, lipopolysaccharide (LPS), CpG oligodeoxynucleotide (CpG-ODN))...
October 18, 2016: Cytokine
Guoying Deng, Fei Zhang, Shufeng Yang, Jian Kang, Shanshan Sha, Yufang Ma
Tuberculosis remains a global major problem. The immune responses of host against Mycobacterium tuberculosis (M. tuberculosis) are complicated. M. tuberculosis lives mainly within host cells, usually macrophages which constitute the first line of host defense. Mycobacterial proteins, especially cell wall-associated proteins, interact with macrophages of host to regulate the functions and cytokine production. Recent studies indicate that glycoproteins are involved in this process. Here, we investigated the function of Rv0431, a cell wall-associated protein in the M...
October 18, 2016: Microbial Pathogenesis
Jin Kyung Kim, Hye-Mi Lee, Ki-Sun Park, Dong-Min Shin, Tae Sung Kim, Yi Sak Kim, Hyun-Woo Suh, Soo Yeon Kim, In Soo Kim, Jin-Man Kim, Ji-Woong Son, Kyung Mok Sohn, Sung Soo Jung, Chaeuk Chung, Sang-Bae Han, Chul-Su Yang, Eun-Kyeong Jo
Autophagy is an important antimicrobial effector process that defends against Mycobacterium tuberculosis (Mtb), the human pathogen causing tuberculosis (TB). MicroRNAs (miRNAs), endogenous noncoding RNAs, are involved in various biological functions and act as post-transcriptional regulators to target mRNAs. The process by which miRNAs affect antibacterial autophagy and host defense mechanisms against Mtb infections in human monocytes and macrophages is largely uncharacterized. In this study, we show that Mtb significantly induces the expression of MIR144*/hsa-miR-144-5p, which targets the 3'-untranslated region of DRAM2 (DNA damage regulated autophagy modulator 2) in human monocytes and macrophages...
October 20, 2016: Autophagy
Gina Leisching, Ray-Dean Pietersen, Carel van Heerden, Paul van Helden, Ian Wiid, Bienyameen Baker
The distinguishing factors that characterize the host response to infection with virulent Mycobacterium tuberculosis (M.tb) are largely confounding. We present an infection study with two genetically closely related M.tb strains that have vastly different pathogenic characteristics. The early host response to infection with these detergent-free cultured strains was analysed through RNAseq in an attempt to provide information on the subtleties which may ultimately contribute to the virulent phenotype. Murine bone marrow derived macrophages (BMDMs) were infected with either a hyper- (R5527) or hypovirulent (R1507) Beijing M...
October 20, 2016: Virulence
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
Mark R Cronan, Rebecca W Beerman, Allison F Rosenberg, Joseph W Saelens, Matthew G Johnson, Stefan H Oehlers, Dana M Sisk, Kristen L Jurcic Smith, Neil A Medvitz, Sara E Miller, Le A Trinh, Scott E Fraser, John F Madden, Joanne Turner, Jason E Stout, Sunhee Lee, David M Tobin
Mycobacterium tuberculosis infection in humans triggers formation of granulomas, which are tightly organized immune cell aggregates that are the central structure of tuberculosis. Infected and uninfected macrophages interdigitate, assuming an altered, flattened appearance. Although pathologists have described these changes for over a century, the molecular and cellular programs underlying this transition are unclear. Here, using the zebrafish-Mycobacterium marinum model, we found that mycobacterial granuloma formation is accompanied by macrophage induction of canonical epithelial molecules and structures...
October 18, 2016: Immunity
J M Greene, P Dash, S Roy, C McMurtrey, W Awad, J S Reed, K B Hammond, S Abdulhaqq, H L Wu, B J Burwitz, B F Roth, D W Morrow, J C Ford, G Xu, J Y Bae, H Crank, A W Legasse, T H Dang, H Y Greenaway, M Kurniawan, M C Gold, M J Harriff, D A Lewinsohn, B S Park, M K Axthelm, J J Stanton, S G Hansen, L J Picker, V Venturi, W Hildebrand, P G Thomas, D M Lewinsohn, E J Adams, J B Sacha
Studies on mucosal-associated invariant T cells (MAITs) in nonhuman primates (NHP), a physiologically relevant model of human immunity, are handicapped due to a lack of macaque MAIT-specific reagents. Here we show that while MR1 ligand-contact residues are conserved between human and multiple NHP species, three T-cell receptor contact-residue mutations in NHP MR1 diminish binding of human MR1 tetramers to macaque MAITs. Construction of naturally loaded macaque MR1 tetramers facilitated identification and characterization of macaque MR1-binding ligands and MAITs, both of which mirrored their human counterparts...
October 19, 2016: Mucosal Immunology
Ann Vu, Andrew Calzadilla, Sanaz Gidfar, Rafael Calderon-Candelario, Mehdi Mirsaeidi
Toll-like receptors are transmembrane glycoproteins predominantly expressed in tissues with immune function. They are considered one of the most important pattern recognition receptor families discovered at the end of 20(th) century and a key aspect of the innate immune system response to infectious disease. Here we present a review of the current knowledge of individual Toll-like receptors, 1 through 13, with a focus on their role in the immune system response to mycobacterial infection. We present literature to date about the Toll-like receptors structure, localization and expression, signaling pathways, and function...
October 15, 2016: European Journal of Pharmacology
Patricia Rubio Reyes, Natalie A Parlane, D Neil Wedlock, Bernd H A Rehm
Traditional approaches to vaccine development have failed to identify better vaccines to replace or supplement BCG for the control of tuberculosis (TB). Subunit vaccines offer a safer and more reproducible alternative for the prevention of diseases. In this study, the immunogenicity of bacterially derived polyester beads displaying three different Rv antigens of Mycobacterium tuberculosis was evaluated. Polyester beads displaying the antigens Rv1626, Rv2032, Rv1789, respectively, were produced in an endotoxin-free Escherichia coli strain...
October 13, 2016: International Journal of Medical Microbiology: IJMM
Isabelle Viel-Thériault, Roseline Thibeault, Francois D Boucher, Jean-Philippe Drolet
Paradoxical immune reconstitution inflammatory syndrome is a well-described entity even in immunocompetent children, principally in association with Mycobacterium tuberculosis infections. Central nervous system involvement is a potential life-threatening form, sometimes refractory to standard treatment. We report the case of an HIV-negative refugee teenager, who presented with brain tuberculomas and pseudoabscesses responsive only to thalidomide.
November 2016: Pediatric Infectious Disease Journal
Himanshu Pandey, Sarita Tripathi, Kanchan Srivastava, Dinesh K Tripathi, Mrigank Srivastava, Surya Kant, Kishore K Srivastava, Ashish Arora
BACKGROUND: We have characterized two immunogenic proteins, Rv1197 and Rv1198, of the Esx-5 system of the ESAT-6 family of Mycobacterium tuberculosis H37Rv. METHODS: The complex formation between Rv1197 and Rv1198 was characterized by biophysical techniques. The reactivity of serum from TB patients towards these proteins was characterized by ELISA. Lymphocyte proliferation and cytokine induction were followed in restimulated splenocytes from immunized mice by using MTT assay and CBA flowcytometry, respectively...
October 14, 2016: Biochimica et Biophysica Acta
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
Marie-Odile Husson, Delphine Ley, Céline Portal, Madeleine Gottrand, Thomas Hueso, Jean-Luc Desseyn, Frédéric Gottrand
OBJECTIVES: Although n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) are used widely in the treatment of chronic inflammatory diseases, their effect in infectious disease requires a particular attention. METHODS: The present article discusses their anti-inflammatory and immune properties involved in the host defence and presents a systematic review of the effects of their oral administration on the prevention and outcome of experimental and clinical infections...
October 14, 2016: Journal of Infection
Arshad Khan, Robert L Hunter, Chinnaswamy Jagannath
Mesenchymal stem cells (MSCs) are non-hematopoietic cells that occur in almost all human tissues and can be cultured and expanded to large numbers in vitro. They secrete growth factors, cytokines, and chemokines and express Toll-like receptors on their surface, although multiple cell biological mechanisms remain unclear. MSCs are multi-potent and can differentiate into many cell types including adipocytes, neuronal cells and osteoclasts. Despite gaps in cell biology, because of their immunomodulatory and regenerative capacity, several hundred clinical trials have used MSCs for therapy of cancer, autoimmune diseases and control of inflammation during organ transplantation...
September 28, 2016: Tuberculosis
Buka Samten, Stewart Fannin, Krishna Sarva, Na Yi, Murty Madiraju, Malini Rajagopalan
Mycobacterium tuberculosis secretes a number of proteins into the extracellular milieu during growth. Several of these proteins have been associated with modulation of the host immune response. Antigen 84, or Wag31, is one such protein that is conserved among all mycobacterial species and is recognized by the sera from tuberculosis and leprosy patients. Here, we examined the effect of Wag31 on the ability of activated human T cells to produce cytokines such as IL-10, IL-17 and IFN-γ in response to combined anti-CD3 and anti-CD28 stimulation...
September 28, 2016: Tuberculosis
Thomas J Scriba, Anna K Coussens, Helen A Fletcher
Immunology is a central theme when it comes to tuberculosis (TB). The outcome of human infection with Mycobacterium tuberculosis is dependent on the ability of the immune response to clear or contain the infection.In cases where this fails, the bacterium replicates, disseminates within the host, and elicits a pathologic inflammatory response, and disease ensues. Clinical presentation of TB disease is remarkably heterogenous, and the disease phenotype is largely dependent on host immune status. Onward transmission of M...
October 2016: Microbiology Spectrum
Ashley V Veatch, Tianhua Niu, John Caskey, Amanda McGillivray, Uma Shankar Gautam, Ramesh Subramanian, K Gus Kousoulas, Smriti Mehra, Deepak Kaushal
Mycobacterium tuberculosis (Mtb) infections cause tuberculosis (TB), an infectious disease which causes ∼1.5 million deaths annually. The ability of this pathogen to evade, escape and encounter immune surveillance is fueled by its adaptability. Thus, Mtb induces a transition in its transcriptome in response to environmental changes. Global transcriptome profiling has been key to our understanding of how Mtb responds to the different stress conditions it faces during its life cycle. While this was initially achieved using microarray technology, RNAseq is now widely employed...
September 28, 2016: Tuberculosis
Shen-An Hwang, Marian L Kruzel, Jeffrey K Actor
Lactoferrin, an iron-binding glycoprotein found in mammalian mucosal secretions and granules of neutrophils, possesses several immune modulatory properties. Published reports indicate that lactoferrin enhances the efficacy of the tuberculosis vaccine, BCG (Bacillus Calmette Guerin), both by increasing macrophage and dendritic cell ability to stimulate receptive T cells and by modulating the inflammatory response. This report is the first to demonstrate the effects of a recombinant human lactoferrin (10 μg/mL) on human PBMC derived CD14(+) and CD16(+) macrophages stimulated with a strong (LPS, 10 ng/mL) or weaker (BCG, MOI 1:1) stimulator of inflammation...
September 28, 2016: Tuberculosis
Patricia J Simner, Gail L Woods, Nancy L Wengenack
The immunocompromised host is at increased risk of Mycobacterium tuberculosis complex and nontuberculous mycobacteria infection. Although Mycobacterium tuberculosis complex is a significant mycobacterial pathogen, nontuberculous mycobacteria causes substantial disease in those with suppressed immune responses. Mycobacterial infections can cause significant morbidity and mortality in this patient population, and rapid identification and susceptibility testing of the mycobacterial species is paramount to patient management and outcomes...
August 2016: Microbiology Spectrum
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