BIOMAT Database Logo BIOMAT Database Logo

Phagosomal processing of Mycobacterium tuberculosis antigen 85B is modulated independently of mycobacterial viability and phagosome maturation. 2005

Lakshmi Ramachandra, and Jamie L Smialek, and Sam S Shank, and Marilyn Convery, and W Henry Boom, and Clifford V Harding
Department of Pediatrics, Case Western Reserve University and Rainbow Babies and Children's Hospital, Room 4007, 11100 Euclid Avenue, Cleveland, OH 44106-6008B, USA. lxr2@cwru.edu

Control of Mycobacterium tuberculosis infection requires CD4 T-cell responses and major histocompatibility complex class II (MHC-II) processing of M. tuberculosis antigens (Ags). We have previously demonstrated that macrophages process heat-killed (HK) M. tuberculosis more efficiently than live M. tuberculosis. These observations suggested that live M. tuberculosis may inhibit Ag processing by inhibiting phagosome maturation or that HK M. tuberculosis may be less resistant to Ag processing. In the present study we examined the correlation between M. tuberculosis viability and phagosome maturation and efficiency of Ag processing. Since heat treatment could render M. tuberculosis Ags more accessible to proteolysis, M. tuberculosis was additionally killed by antibiotic treatment and radiation. Processing of HK, live, radiation-killed (RadK), or rifampin-killed (RifK) M. tuberculosis in activated murine bone marrow macrophages was examined by using an I-A(b)-restricted T-cell hybridoma cell line (BB7) that recognizes an epitope derived from Ag 85B. Macrophages processed HK M. tuberculosis more rapidly and efficiently than they processed live, RadK, or RifK M. tuberculosis. Live, RadK, and RifK M. tuberculosis cells were processed with similar efficiencies for presentation to BB7 T hybridoma cells. Furthermore, phagosomes containing live or RadK M. tuberculosis expressed fewer M. tuberculosis peptide-MHC-II complexes than phagosomes containing HK M. tuberculosis expressed. Since only live M. tuberculosis was able to prevent acidification of the phagosome, our results suggest that regulation of phagosome maturation does not explain the differences in processing of different forms of M. tuberculosis. These findings suggest that the mechanisms used by M. tuberculosis to inhibit phagosomal maturation differ from the mechanisms involved in modulating phagosome Ag processing.

UI MeSH Term Description Entries
D009169 Mycobacterium tuberculosis A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation. Mycobacterium tuberculosis H37Rv
D010588 Phagosomes Membrane-bound cytoplasmic vesicles formed by invagination of phagocytized material. They fuse with lysosomes to form phagolysosomes in which the hydrolytic enzymes of the lysosome digest the phagocytized material. Phagolysosomes,Phagolysosome,Phagosome
D000217 Acyltransferases Enzymes from the transferase class that catalyze the transfer of acyl groups from donor to acceptor, forming either esters or amides. (From Enzyme Nomenclature 1992) EC 2.3. Acyltransferase
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000904 Antibiotics, Antitubercular Substances obtained from various species of microorganisms that are, alone or in combination with other agents, of use in treating various forms of tuberculosis; most of these agents are merely bacteriostatic, induce resistance in the organisms, and may be toxic. Antitubercular Antibiotics
D000942 Antigens, Bacterial Substances elaborated by bacteria that have antigenic activity. Bacterial Antigen,Bacterial Antigens,Antigen, Bacterial
D001426 Bacterial Proteins Proteins found in any species of bacterium. Bacterial Gene Products,Bacterial Gene Proteins,Gene Products, Bacterial,Bacterial Gene Product,Bacterial Gene Protein,Bacterial Protein,Gene Product, Bacterial,Gene Protein, Bacterial,Gene Proteins, Bacterial,Protein, Bacterial,Proteins, Bacterial
D012293 Rifampin A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160) Rifampicin,Benemycin,Rifadin,Rimactan,Rimactane,Tubocin
D014376 Tuberculosis Any of the infectious diseases of man and other animals caused by species of MYCOBACTERIUM TUBERCULOSIS. Koch's Disease,Kochs Disease,Mycobacterium tuberculosis Infection,Infection, Mycobacterium tuberculosis,Infections, Mycobacterium tuberculosis,Koch Disease,Mycobacterium tuberculosis Infections,Tuberculoses
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

Related Publications

Lakshmi Ramachandra, and Jamie L Smialek, and Sam S Shank, and Marilyn Convery, and W Henry Boom, and Clifford V Harding
Characterization of the Mycobacterium tuberculosis phagosome and evidence that phagosomal maturation is inhibited.
January 1995, The Journal of experimental medicine,
Lakshmi Ramachandra, and Jamie L Smialek, and Sam S Shank, and Marilyn Convery, and W Henry Boom, and Clifford V Harding
Processing of Mycobacterium tuberculosis antigen 85B involves intraphagosomal formation of peptide-major histocompatibility complex II complexes and is inhibited by live bacilli that decrease phagosome maturation.
November 2001, The Journal of experimental medicine,
Lakshmi Ramachandra, and Jamie L Smialek, and Sam S Shank, and Marilyn Convery, and W Henry Boom, and Clifford V Harding
Human phagosome processing of Mycobacterium tuberculosis antigens is modulated by interferon-γ and interleukin-10.
January 2013, Immunology,
Lakshmi Ramachandra, and Jamie L Smialek, and Sam S Shank, and Marilyn Convery, and W Henry Boom, and Clifford V Harding
Mycobacterium tuberculosis phagosome maturation arrest: mycobacterial phosphatidylinositol analog phosphatidylinositol mannoside stimulates early endosomal fusion.
February 2004, Molecular biology of the cell,
Lakshmi Ramachandra, and Jamie L Smialek, and Sam S Shank, and Marilyn Convery, and W Henry Boom, and Clifford V Harding
Cellubrevin alterations and Mycobacterium tuberculosis phagosome maturation arrest.
May 2002, The Journal of biological chemistry,
Lakshmi Ramachandra, and Jamie L Smialek, and Sam S Shank, and Marilyn Convery, and W Henry Boom, and Clifford V Harding
Rab14 is critical for maintenance of Mycobacterium tuberculosis phagosome maturation arrest.
November 2006, The EMBO journal,
Lakshmi Ramachandra, and Jamie L Smialek, and Sam S Shank, and Marilyn Convery, and W Henry Boom, and Clifford V Harding
Role of phosphatidylinositol 3-kinase and Rab5 effectors in phagosomal biogenesis and mycobacterial phagosome maturation arrest.
August 2001, The Journal of cell biology,
Lakshmi Ramachandra, and Jamie L Smialek, and Sam S Shank, and Marilyn Convery, and W Henry Boom, and Clifford V Harding
Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest.
April 2003, Proceedings of the National Academy of Sciences of the United States of America,
Lakshmi Ramachandra, and Jamie L Smialek, and Sam S Shank, and Marilyn Convery, and W Henry Boom, and Clifford V Harding
Novel human recombinant antibodies against Mycobacterium tuberculosis antigen 85B.
July 2014, BMC biotechnology,
Lakshmi Ramachandra, and Jamie L Smialek, and Sam S Shank, and Marilyn Convery, and W Henry Boom, and Clifford V Harding
LRRK2 is a negative regulator of Mycobacterium tuberculosis phagosome maturation in macrophages.
June 2018, The EMBO journal,
Copied contents to your clipboard!