Q99562800
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One third of the world's population is latently infected with Mycobacterium tuberculosis (Mtb) and up to 10% of infected individuals develop active tuberculosis (TB) in their lifetime. Among the major challenges in the control of TB is the implementation of sensitive methods for detection of latent tuberculosis infection (LTBI). Currently, in vitro interferon gamma release assays, yielding single value readout, are used as an alternative to the traditional tuberculin skin test for the diagnosis of LTBI. More complex characterization of immune status of LTBI individuals, however, is desirable for indication of LTBI subjects for preventative chemotherapy. Here we describe a quantitative polymerase chain reaction (qPCR) for determination of expression levels of 14 genes, additional to interferon gamma, which was applied for comparison of the specific Mtb-antigen immune response of blood cells from healthy, latently infected, and TB individuals. With the use of principal component analysis and discriminant analysis, a pattern of mRNA levels of 6 genes was identified, allowing discrimination of healthy individuals from active TB and LTBI subjects. These results open the way to development of multimarker qPCR for the detection of LTBI.
- MeSH
- antigeny bakteriální imunologie MeSH
- diagnostické techniky molekulární metody MeSH
- dospělí MeSH
- kvantitativní polymerázová řetězová reakce metody MeSH
- latentní tuberkulóza diagnóza MeSH
- leukocyty mononukleární imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- Mycobacterium tuberculosis imunologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stanovení celkové genové exprese metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
Adenylate cyclase toxin (CyaA or ACT) is a key virulence factor of pathogenic Bordetellae. It penetrates phagocytes expressing the alpha(M)beta(2) integrin (CD11b/CD18, Mac-1 or CR3) and paralyzes their bactericidal capacities by uncontrolled conversion of ATP into a key signaling molecule, cAMP. Using pull-down activity assays and transfections with mutant Rho family GTPases, we show that cAMP signaling of CyaA causes transient and selective inactivation of RhoA in mouse macrophages in the absence of detectable activation of Rac1, Rac2, or RhoG. This CyaA/cAMP-induced drop of RhoA activity yielded dephosphorylation of the actin filament severing protein cofilin and massive actin cytoskeleton rearrangements, which were paralleled by rapidly manifested macrophage ruffling and a rapid and unexpected loss of macropinocytic fluid phase uptake. As shown in this study for the first time, CyaA/cAMP signaling further caused a rapid and near-complete block of complement-mediated phagocytosis. Induction of unproductive membrane ruffling, hence, represents a novel sophisticated mechanism of down-modulation of bactericidal activities of macrophages and a new paradigm for action of bacterial toxins that hijack host cell signaling by manipulating cellular cAMP levels.
- MeSH
- adenylátcyklasový toxin imunologie metabolismus MeSH
- AMP cyklický imunologie MeSH
- antigeny CD11b genetika imunologie MeSH
- antigeny CD18 genetika imunologie MeSH
- Bordetella pertussis enzymologie imunologie MeSH
- buněčná membrána imunologie metabolismus MeSH
- buněčné linie MeSH
- faktory depolymerizující aktin imunologie metabolismus MeSH
- financování organizované MeSH
- GTP-fosfohydrolasy imunologie metabolismus MeSH
- makrofágový antigen 1 imunologie metabolismus MeSH
- makrofágy imunologie metabolismus MeSH
- mikrofilamenta imunologie metabolismus MeSH
- myši MeSH
- neuropeptidy imunologie metabolismus MeSH
- pertuse enzymologie imunologie MeSH
- rac proteiny vázající GTP imunologie metabolismus MeSH
- rho proteiny vázající GTP imunologie metabolismus MeSH
- signální transdukce imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
Neisseria meningitidis colonizes the human nasopharynx and occasionally causes lethal or damaging septicemia and meningitis. Here, we examined the adherence-mediated signaling of meningococci to human cells by comparing gene expression profiles of human umbilical vein endothelial cells (HUVEC) infected by adherent wild-type, frpC-deficient mutant, or the nonadherent (DeltapilD) N. meningitidis. Pili-mediated adhesion of meningococci resulted in alterations of expression levels of human genes known to regulate apoptosis, cell proliferation, inflammatory response, adhesion and genes for signaling pathway proteins such as TGF-beta/Smad, Wnt/beta-catenin and Notch/Jagged. This reveals that adhering piliated meningocci manipulate host signaling pathways controlling cell proliferation while establishing a commensal relationship.
- MeSH
- apoptóza imunologie MeSH
- bakteriální adheze MeSH
- bakteriální proteiny genetika MeSH
- buněčné kultury MeSH
- cytoprotekce genetika MeSH
- embryo savčí metabolismus MeSH
- endoteliální buňky mikrobiologie MeSH
- financování organizované MeSH
- lidé MeSH
- membránové proteiny genetika nedostatek MeSH
- Neisseria meningitidis patogenita MeSH
- proteiny fimbrií genetika nedostatek MeSH
- průtoková cytometrie MeSH
- RNA komplementární MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- signální transdukce MeSH
- stanovení celkové genové exprese MeSH
- upregulace MeSH
- venae umbilicales cytologie MeSH
- zánět genetika MeSH
- Check Tag
- lidé MeSH
- MeSH
- bakteriální proteiny genetika metabolismus MeSH
- lipoproteiny genetika metabolismus MeSH
- membránové proteiny genetika chemie metabolismus MeSH
- Neisseria meningitidis genetika MeSH
- proteiny vnější bakteriální membrány genetika metabolismus MeSH
- techniky in vitro MeSH
- vápník farmakologie MeSH
- železo metabolismus MeSH
- MeSH
- bakteriální proteiny genetika MeSH
- bakteriemie mikrobiologie mortalita MeSH
- cytotoxiny genetika metabolismus MeSH
- finanční podpora výzkumu jako téma MeSH
- krysa rodu rattus MeSH
- meningokokové infekce mortalita MeSH
- Neisseria meningitidis metabolismus patogenita MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
