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      The role of dendritic cells in Mycobacterium tuberculosis infection

      review-article
      1 , 2 , *
      Virulence
      Landes Bioscience
      M. tuberculosis, dendritic cells, maturation, activation, T cells

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          Abstract

          The immune response against Mycobacterium tuberculosis is multifactorial, involving a network of innate and adaptive immune responses. Characterization of the immune response, a clear understanding of the dynamics and interplay of different arms of the immune response are critical to allow the development of better tools for combating tuberculosis. Dendritic cells (DCs) are one of the key cells in bridging innate and adaptive immune response through their significant role in capturing, processing and presenting antigens. The outcome of interaction of M. tuberculosis with DCs is not fully understood and the available reports are contradictory were some findings reported that DCs strengthen the cellular immune response against mycobacterium infection whereas others reported M. tuberculosis impairs the function of DCs were infected DCs are poor stimulators of M. tuberculosis Ag-specific CD4 T cells. Other studies showed that the outcome depends on M. tuberculosis strain type and type of receptor on DCs during recognition. In this review I shall highlight the recent findings in the outcome of interaction of Mycobacterium tuberculosis with DCs.

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          Most cited references79

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          Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice.

          Understanding the immunological mechanisms of protection and pathogenesis in tuberculosis remains problematic. We have examined the extent to which tumor necrosis factor-alpha (TNF alpha) contributes to this disease using murine models in which the action of TNF alpha is inhibited. TNF alpha was neutralized in vivo by monoclonal antibody; in addition, a mouse strain with a disruption in the gene for the 55 kDa TNF receptor was used. The data from both models established that TNF alpha and the 55 kDa TNF receptor are essential for protection against tuberculosis in mice, and for reactive nitrogen production by macrophages early in infection. Granulomas were formed in equal numbers in control and experimental mice, but necrosis was observed only in mice deficient in TNF alpha or TNF receptor. TNF alpha and the 55 kDa TNF receptor are necessary conditions for protection against murine M. tuberculosis infection, but are not solely responsible for the tissue damage observed.
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            IRF8 mutations and human dendritic-cell immunodeficiency.

            The genetic analysis of human primary immunodeficiencies has defined the contribution of specific cell populations and molecular pathways in the host defense against infection. Disseminated infection caused by bacille Calmette-Guérin (BCG) vaccines is an early manifestation of primary immunodeficiencies, such as severe combined immunodeficiency. In many affected persons, the cause of disseminated BCG disease is unexplained. We evaluated an infant presenting with features of severe immunodeficiency, including early-onset disseminated BCG disease, who required hematopoietic stem-cell transplantation. We also studied two otherwise healthy subjects with a history of disseminated but curable BCG disease in childhood. We characterized the monocyte and dendritic-cell compartments in these three subjects and sequenced candidate genes in which mutations could plausibly confer susceptibility to BCG disease. We detected two distinct disease-causing mutations affecting interferon regulatory factor 8 (IRF8). Both K108E and T80A mutations impair IRF8 transcriptional activity by disrupting the interaction between IRF8 and DNA. The K108E variant was associated with an autosomal recessive severe immunodeficiency with a complete lack of circulating monocytes and dendritic cells. The T80A variant was associated with an autosomal dominant, milder immunodeficiency and a selective depletion of CD11c+CD1c+ circulating dendritic cells. These findings define a class of human primary immunodeficiencies that affect the differentiation of mononuclear phagocytes. They also show that human IRF8 is critical for the development of monocytes and dendritic cells and for antimycobacterial immunity. (Funded by the Medical Research Council and others.).
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              Initiation of the adaptive immune response to Mycobacterium tuberculosis depends on antigen production in the local lymph node, not the lungs

              The onset of the adaptive immune response to Mycobacterium tuberculosis is delayed compared with that of other infections or immunization, and allows the bacterial population in the lungs to expand markedly during the preimmune phase of infection. We used adoptive transfer of M. tuberculosis Ag85B-specific CD4+ T cells to determine that the delayed adaptive response is caused by a delay in initial activation of CD4+ T cells, which occurs earliest in the local lung-draining mediastinal lymph node. We also found that initial activation of Ag85B-specific T cells depends on production of antigen by bacteria in the lymph node, despite the presence of 100-fold more bacteria in the lungs. Although dendritic cells have been found to transport M. tuberculosis from the lungs to the local lymph node, airway administration of LPS did not accelerate transport of bacteria to the lymph node and did not accelerate activation of Ag85B-specific T cells. These results indicate that delayed initial activation of CD4+ T cells in tuberculosis is caused by the presence of the bacteria in a compartment that cannot be mobilized from the lungs to the lymph node, where initial T cell activation occurs.
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                Author and article information

                Journal
                Virulence
                Virulence
                VIRU
                Virulence
                Landes Bioscience
                2150-5594
                2150-5608
                15 November 2012
                15 November 2012
                : 3
                : 7
                : 654-659
                Affiliations
                [1 ]Armauer Hansen Research Institute; Addis Ababa, Ethiopia
                [2 ]Department of Microbiology, Immunology and Parasitology; College of Health Sciences; School of Medicine; Addis Ababa University; Addis Ababa, Ethopia
                Author notes
                [* ]Correspondence to: Adane Mihret, Email: adane_mihret@ 123456yahoo.com
                Article
                2012VIRULENCE0041R1 22586
                10.4161/viru.22586
                3545947
                23154283
                1afbf9cf-73c5-45b1-9b6a-9c776efcde0f
                Copyright © 2012 Landes Bioscience

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                : 24 July 2012
                : 03 September 2012
                : 18 October 2012
                Categories
                Review

                Infectious disease & Microbiology
                m. tuberculosis,t cells,activation,dendritic cells,maturation
                Infectious disease & Microbiology
                m. tuberculosis, t cells, activation, dendritic cells, maturation

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