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Interferon research abs 1 || Hemoglobin research abs || Stem cell research abs || Nucleic acid research abs || Herpes research abs || Bronchitis research abs || Schizophrenia research abs || Tuberculosis research abs

Am J Respir Cell Mol Biol. 2001 Feb;24(2):203-9.
CD8- and CD95/95L-dependent mechanisms of resistance in mice with chronic pulmonary tuberculosis.

Turner J, D'Souza CD, Pearl JE, Marietta P, Noel M, Frank AA, Appelberg R, Orme IM, Cooper AM.

Mycobacterial Research Laboratories, Colorado State University, 200 W. Lake, Fort Collins, CO 80523, USA.

The role of CD8 T lymphocytes in the immune response to Mycobacterium tuberculosis infection remains enigmatic, with persuasive reports of both cytolytic and noncytolytic (cytokine-mediated) responses to infection. To address the importance of the cytolytic mechanisms, mice with targeted disruptions for CD8 and perforin or with gene mutations in the CD95/ CD95L signaling pathway were exposed to pulmonary infection. All mice tested showed no differences in their ability to contain the growth of infection during the early phase of disease. As the chronic phase of the disease ensued, however, both CD8- and CD95/CD95L-deficient mice gradually lost their ability to limit bacterial growth. This was associated with a tendency toward pyogenic inflammation in the lung. This tendency was not seen in the perforin gene-disrupted mice. In CD8 gene-disrupted mice, the ability to generate interferon-gamma secreting T cells was unimpaired. Although these cells were capable of entering the lung they were unable to influence the increasing bacterial load in this organ.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11159055&dopt=Abstract

Am J Pathol. 2001 Feb;158(2):361-6.
Disruption of nuclear factor-interleukin-6, a transcription factor, results in severe mycobacterial infection.

Sugawara I, Mizuno S, Yamada H, Matsumoto M, Akira S.

Department of Molecular Pathology, The Research Institute of Tuberculosis, Kiyose, Tokyo, Japan. sugawarata.or.jp

Nuclear factor-interleukin-6 (NF-IL-6) is one of several nuclear transcription factors (NF-IL-6, NF-kappaB, PU.1, interferon-regulatory factor 1, Egr-1, and Stat-1). NF-IL-6 and NF-kappaB are expressed in macrophages and is induced by bacterial lipopolysaccharides. To evaluate whether NF-IL-6 is required for the inflammatory immune response to mycobacterial infection, in which epithelioid macrophages comprise the leading cell population, we generated NF-IL-6 knockout (KO) mutant mice. Airborne infection of these mice with Mycobacterium tuberculosis strains induced disseminated tuberculosis lacking granuloma formation, although interferon-gamma, tumor necrosis factor-alpha, and interleukin-12 mRNA expression levels were within the normal range compared with those of wild-type mice. Generation of O2- and mycobacterial killing by neutrophils from these mice were impaired severely compared with wild-type mice. We conclude that NF-IL-6 is a critical transcription factor in mycobacterial control as well as in granulocyte-colony stimulating factor induction resulting in neutrophil activation.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11159172&dopt=Abstract

Arch Dis Child. 2001 Feb;84(2):109-13.
Tuberculosis, deprivation, and ethnicity in Leeds, UK, 1982-1997.

Parslow R, El-Shimy NA, Cundall DB, McKinney PA.

Paediatric Epidemiology Group, Institute of Epidemiology, University of Leeds, 32 Hyde Terrace, Leeds LS2 9LN, UK.

AIMS: To determine whether tuberculosis is increasing in frequency and to explore the association between deprivation, ethnicity, and tuberculosis in the city of Leeds. METHODS: Descriptive epidemiology and ecological analysis of a register of children and young people (0-18 years) diagnosed with tuberculosis from 1982 to 1997 in Leeds Health Authority. RESULTS: A total of 107 children were identified, 61 through contact tracing, to give an age and sex standardised incidence rate of 3.9 per 100 000 per year. Rates decreased over the 16 year study period by an estimated 6.6% per year. The disease was more common in girls (56%) and most frequent in 5-9 year olds, with respiratory disease accounting for the largest proportion (82%). Children of south Asian origin (35%) had a crude incidence rate of 25.7 per 100 000 per year. The female:male ratios differed notably between south Asian (1.9:1) and non-south Asian children (1.02:1). For all subjects, univariate analyses showed significant positive associations between incidence and deprivation, population density, and ethnicity. There were no significant associations between deprivation, population density, and ethnicity and incidence of tuberculosis in south Asian children. For non-south Asian, mainly white children, only deprivation was significant. The proportion of non-south Asian children in the population was the overriding factor influencing incidence of tuberculosis. CONCLUSIONS: Tuberculosis remains an uncommon disease in Leeds children. An unexpected finding was a relatively higher incidence in Asian girls compared to boys. Overall, ethnicity explains a high proportion of disease independently of deprivation and population density but for non-south Asian Leeds children the strongest risk factor is deprivation.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11159282&dopt=Abstract

Infect Immun. 2001 Feb;69(2):681-6. ["Cited in Books","window.top.location='/entrez/query.fcgi?tool=pmcited&cmd=search&db=books&term=11159955[pmid]'","",""],
Enhanced immunogenicity of CD4(+) t-cell responses and protective efficacy of a DNA-modified vaccinia virus Ankara prime-boost vaccination regimen for murine tuberculosis.

McShane H, Brookes R, Gilbert SC, Hill AV.

Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. helen.mcshandm.ox.ac.uk

DNA vaccines whose DNA encodes a variety of antigens from Mycobacterium tuberculosis have been evaluated for immunogenicity and protective efficacy. CD8(+) T-cell responses and protection achieved in other infectious disease models have been optimized by using a DNA immunization to prime the immune system and a recombinant virus encoding the same antigen(s) to boost the response. A DNA vaccine (D) and recombinant modified vaccinia virus Ankara (M) in which the DNA encodes early secreted antigenic target 6 and mycobacterial protein tuberculosis 63 synthesized, and each was found to generate specific gamma interferon (IFN-gamma)-secreting CD4(+) T cells. Enhanced CD4(+) IFN-gamma T-cell responses were produced by both D-M and M-D immunization regimens. Significantly higher levels of IFN-gamma were seen with a D-D-D-M immunization regimen. The most immunogenic regimens were assessed in a challenge study and found to produce protection equivalent to that produced by Mycobacterium bovis BCG. Thus, heterologous prime-boost regimens boost CD4(+) as well as CD8(+) T-cell responses, and the use of heterologous constructs encoding the same antigen(s) may improve the immunogenicity and protective efficacy of DNA vaccines against tuberculosis and other diseases.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11159955&dopt=Abstract

Infect Immun. 2001 Feb;69(2):800-9.
Fate of Mycobacterium tuberculosis within murine dendritic cells.

Bodnar KA, Serbina NV, Flynn JL.

Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.

The interaction of microbes with dendritic cells (DCs) is likely to have an enormous impact on the initiation of the immune response against a pathogen. In this study, we compared the interaction of Mycobacterium tuberculosis with murine bone marrow-derived DCs and macrophages (M phi) in vitro. M. tuberculosis grew equally well within nonactivated DCs and M phi. Activation of DCs and M phi with gamma interferon and lipopolysaccharide inhibited the growth of the intracellular bacteria in a nitric oxide synthase-dependent fashion. However, while this activation enabled M phi to kill the intracellular bacteria, the M. tuberculosis bacilli within activated DCs were not killed. Thus, DCs could restrict the growth of the intracellular mycobacteria but were less efficient than M phi at eliminating the infection. These results may have implications for priming immune responses to M. tuberculosis. In addition, they suggest that DCs may serve as a reservoir for M. tuberculosis in tissues, including the lymph nodes and lungs.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11159971&dopt=Abstract

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