Phosphatidylmyo-inositol mannosides

Last updated

Phosphatidylmyo-inositol Mannosides (PIMs) are a family of glycolipids found in the cell wall of Mycobacterium tuberculosis . PIMs influence the interaction of the immune system with M. tuberculosis, and mice that develop antibodies for this family of glycolipids are better at sustaining or defeating a M. tuberculosis infection. [1] [2] Thus, PIMs are important glycolipids associated with M. tuberculosis, but are also likely involved with the process by which M. tuberculosis subverts the immune system. [3] [4] [5] [6] [7]

<i>Mycobacterium tuberculosis</i> Species of bacterium

Mycobacterium tuberculosis is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, M. tuberculosis has an unusual, waxy coating on its cell surface primarily due to the presence of mycolic acid. This coating makes the cells impervious to Gram staining, and as a result, M. tuberculosis can appear either Gram-negative or Gram-positive. Acid-fast stains such as Ziehl-Neelsen, or fluorescent stains such as auramine are used instead to identify M. tuberculosis with a microscope. The physiology of M. tuberculosis is highly aerobic and requires high levels of oxygen. Primarily a pathogen of the mammalian respiratory system, it infects the lungs. The most frequently used diagnostic methods for tuberculosis are the tuberculin skin test, acid-fast stain, culture, and polymerase chain reaction.

Immune system A biological system that protects an organism against disease

The immune system is a host defense system comprising many biological structures and processes within an organism that protects against disease. To function properly, an immune system must detect a wide variety of agents, known as pathogens, from viruses to parasitic worms, and distinguish them from the organism's own healthy tissue. In many species, the immune system can be classified into subsystems, such as the innate immune system versus the adaptive immune system, or humoral immunity versus cell-mediated immunity. In humans, the blood–brain barrier, blood–cerebrospinal fluid barrier, and similar fluid–brain barriers separate the peripheral immune system from the neuroimmune system, which protects the brain.

Antibody large Y-shaped protein produced by B-cells, used by the immune system; large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to neutralize pathogens such as pathogenic bacteria and viruses

An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to neutralize pathogens such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen, via the fragment antigen-binding (Fab) variable region. Each tip of the "Y" of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize its target directly. Depending on the antigen, the binding may impede the biological process causing the disease or may activate macrophages to destroy the foreign substance. The ability of an antibody to communicate with the other components of the immune system is mediated via its Fc region, which contains a conserved glycosylation site involved in these interactions. The production of antibodies is the main function of the humoral immune system.

Related Research Articles

<i>Mycobacterium smegmatis</i> species of bacterium

Mycobacterium smegmatis is an acid-fast bacterial species in the phylum Actinobacteria and the genus Mycobacterium. It is 3.0 to 5.0 µm long with a bacillus shape and can be stained by Ziehl-Neelsen method and the auramine-rhodamine fluorescent method. It was first reported in November 1884 by Lustgarten, who found a bacillus with the staining appearance of tubercle bacilli in syphilitic chancres. Subsequent to this, Alvarez and Tavel found organisms similar to that described by Lustgarten also in normal genital secretions (smegma). This organism was later named M. smegmatis.

Phagosome

In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs). A phagosome is formed by the fusion of the cell membrane around a microorganism, a senescent cell or an apoptotic cell. Phagosomes have membrane-bound proteins to recruit and fuse with lysosomes to form mature phagolysosomes. The lysosomes contain hydrolytic enzymes and reactive oxygen species (ROS) which kill and digest the pathogens. Phagosomes can also form in non-professional phagocytes, but they can only engulf a smaller range of particles, and do not contain ROS. The useful materials from the digested particles are moved into the cytosol, and waste is removed by exocytosis. Phagosome formation is crucial for tissue homeostasis and both innate and adaptive host defense against pathogens.

CD1 is a family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are related to the class I MHC molecules, and are involved in the presentation of lipid antigens to T cells. However their precise function is unknown.

rBCG30 is a prospective vaccine against tuberculosis created by a team headed by Marcus A. Horwitz at UCLA. It is a live vaccine, consisting of BCG genetically modified to produce abundant amounts of a 30kDa antigen that has been shown to produce a strong immune response in animals and humans. The vaccine completed a Phase I double-blind randomized controlled clinical trial that demonstrated that rBCG30 was safe and immunogenic; during nine months of follow-up, rBCG30, but not BCG, induced significantly increased Antigen 85B-specific immune responses in eight immunological assays.

Lipoarabinomannan, also called LAM, is a glycolipid, and a virulence factor associated with Mycobacterium tuberculosis, the bacteria responsible for tuberculosis. Its primary function is to inactivate macrophages and scavenge oxidative radicals.

EEA1 protein-coding gene in the species Homo sapiens

The gene EEA1 encodes for the 1400 amino acid protein, Early Endosome Antigen 1.

T-SPOT.TB is a type of ELISpot Assay used for tuberculosis diagnosis, which belongs to the group of interferon gamma release assays. The test is manufactured by Oxford Immunotec in the UK. It is available in most European countries, the United States as well as various other countries. It was developed by researchers at the University of Oxford in England.

Listeriolysin O (LLO) is a hemolysin produced by the bacterium Listeria monocytogenes, the pathogen responsible for causing listeriosis. The toxin may be considered a virulence factor, since it is crucial for the virulence of L. monocytogenes.

Vojo Deretic American geneticist

Vojo Deretic, Ph.D., is the director of the NIH-funded Autophagy, Inflammation and Metabolism (AIM) Center of Biomedical Research Excellence. The AIM center aims to promote autophagy research nationally and internationally as well as to develop a cadre of junior faculty along with senior experts in this area to study fundamental mechanisms and how autophagy intersects with a broad spectrum of human disease and health states. Dr. Deretic is the departmental chair of the Department of Molecular Genetics and Microbiology as well as Professor of Molecular Genetics & Microbiology, Cell Biology & Physiology, and Neurology at the University of New Mexico.

IL12A protein-coding gene in the species Homo sapiens

Interleukin-12 subunit alpha is a protein that in humans is encoded by the IL12A gene.

PIK3C3 protein-coding gene in the species Homo sapiens

Phosphatidylinositol 3-kinase catalytic subunit type 3 is an enzyme that in humans is encoded by the PIK3C3 gene.

Thymic stromal lymphopoietin protein-coding gene in the species Homo sapiens

Thymic stromal lymphopoietin (TSLP) is a protein belonging to the cytokine family. It is known to play an important role in the maturation of T cell populations through activation of antigen presenting cells.

Type IV hypersensitivity is often called delayed type hypersensitivity as the reaction takes several days to develop. Unlike the other types, it is not antibody-mediated but rather is a type of cell-mediated response. This response involves the interaction of T-cells, monocytes, and macrophages.

Cord factor

Cord factor, or trehalose dimycolate, is a glycolipid molecule found in the cell wall of Mycobacterium tuberculosis and similar species. It is the primary lipid found on the exterior of M. tuberculosis cells. Cord factor influences the arrangement of M. tuberculosis cells into long and slender formations, giving its name. Cord factor is virulent towards mammalian cells and critical for survival of M. tuberculosis in hosts, but not outside of hosts. Cord factor has been observed to influence immune responses, induce the formation of granulomas, and inhibit tumor growth. The antimycobacterial drug SQ109 is thought to inhibit TDM production levels and in this way disrupts its cell wall assembly.

The antibodies from lymphocyte secretions (ALS) assay is an immunological assay to detect active diseases like tuberculosis, cholera, typhoid etc. Recently, ALS assay nods the scientific community as it is rapidly used for diagnosis of Tuberculosis. The principle is based on the secretion of antibody from in vivo activated plasma B cells found in blood circulation for a short period of time in response to TB-antigens during active TB infection rather than latent TB infection.

IRGs group of proteins

Immunity Related Guanosine Triphosphatases or IRGs are proteins activated as part of an early immune response. IRGs have been described in various mammals but are most well characterized in mice. IRG activation in most cases is induced by an immune response and leads to clearance of certain pathogens.

Macrophage inducible Ca2+-dependent lectin receptor, (abbreviated to Mincle), is a member of the C-type lectin superfamily encoded by the gene CLEC4E. It is a pattern recognition receptor that can recognize glycolipids including mycobacterial cord factor, trehalose-6,6'-dimycolate (TDM). The mincle receptor binds a range of carbohydrate structures, predominantly containing glucose or mannose, and play an important role in recognition of bacterial glycolipids by the immune system. Upon activation by cord factor, Mincle binds the Fc receptor FcRγ and Syk. Cord factor also binds and activates the related C-type lectin MCL.

Isotuberculosinol, also called nosyberkol or edaxadiene is a diterpene molecule produced by the bacterium Mycobacterium tuberculosis, the causative agent of TB, which aids in its pathogenesis. Isotuberculosinol functions by preventing maturation of the host-cell phagosome in which the bacterium lives. Maturation of the phagosome would enable it to kill the bacterium. Mutations in genes involved in the biosynthetic pathway of nosyberkol result in normal development of the phagosome and reduction of mycobacterial infection. These biosynthetic genes include isotuberculosinol synthase.

References

  1. Mehta, P. K., and G. K. Khuller. 1988. Protective immunity to experimental tuberculosis by mannophosphoinositides of mycobacteria. Med. Microbiol. Immunol. (Berlin) 177:265–284.
  2. Singh, A. P., and G. K. Khuller. 1993. Liposomes as a carrier for mannophosphoinositide antigens of mycobacteria. Indian J. Biochem. Biophys. 30:160–165.
  3. Fratti, R. A., J. M. Backer, J. Gruenberg, S. Corvera, and V. Deretic. 2001. Role of phosphatidylinositol 3-kinase and Rab5 effectors in phagosomal biogenesis and mycobacterial phagosome maturation arrest. J. Cell Biol. 154:631–644.
  4. Kaplan, G., R. R. Gandhi, D. E. Weinstein, W. R. Levis, M. E. Patarroyo, P. J. Brennan, and Z. A. Cohn. 1987. Mycobacterium leprae antigen-induced suppression of T cell proliferation in vitro. J. Immunol. 138:3028–3034.
  5. Sibley, L. D., L. B. Adams, and J. L. Krahenbuhl. 1990. Inhibition of interferon-gamma-mediated activation in mouse macrophages treated with lipoarabinomannan. Clin. Exp. Immunol. 80:141–148.
  6. Vergne, I., J. Chua, and V. Deretic. 2003. Tuberculosis toxin blocking phagosome maturation inhibits a novel Ca2!/calmodulin-PI3K hVPS34 cascade. J. Exp. Med. 198:653–659.
  7. Vergne, I., R. A. Fratti, P. J. Hill, J. Chua, J. Belisle, and V. Deretic. 2004. Mycobacterium tuberculosis phagosome maturation arrest: mycobacterial phosphatidylinositol analog phosphatidylinositol mannoside stimulates early endosomal fusion. Mol. Biol. Cell 15:751–760.