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Innate Immune Responses to Tuberculosis

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  • Authors: Jeffrey S. Schorey1, Larry S. Schlesinger2
  • Editors: William R. Jacobs Jr.3, Helen McShane4, Valerie Mizrahi5, Ian M. Orme6
    Affiliations: 1: Department of Biological Sciences, Eck Institute for Global Health, Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556; 2: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210; 3: Howard Hughes Medical Institute, Albert Einstein School of Medicine, Bronx, NY 10461; 4: University of Oxford, Oxford OX3 7DQ, United Kingdom; 5: University of Cape Town, Rondebosch 7701, South Africa; 6: Colorado State University, Fort Collins, CO 80523
  • Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.TBTB2-0010-2016
  • Received 24 January 2016 Accepted 04 February 2016 Published 09 December 2016
  • Larry S. Schlesinger, [email protected]
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  • Abstract:

    Tuberculosis remains one of the greatest threats to human health. The causative bacterium, , is acquired by the respiratory route. It is exquisitely adapted to humans and is a prototypic intracellular pathogen of macrophages, with alveolar macrophages being the primary conduit of infection and disease. However, bacilli interact with and are affected by several soluble and cellular components of the innate immune system which dictate the outcome of primary infection, most commonly a latently infected healthy human host, in whom the bacteria are held in check by the host immune response within the confines of tissue granuloma, the host histopathologic hallmark. Such individuals can develop active TB later in life with impairment in the immune system. In contrast, in a minority of infected individuals, the early host immune response fails to control bacterial growth, and progressive granulomatous disease develops, facilitating spread of the bacilli via infectious aerosols. The molecular details of the -host innate immune system interaction continue to be elucidated, particularly those occurring within the lung. However, it is clear that a number of complex processes are involved at the different stages of infection that may benefit either the bacterium or the host. In this article, we describe a contemporary view of the molecular events underlying the interaction between and a variety of cellular and soluble components and processes of the innate immune system.

  • Citation: Schorey J, Schlesinger L. 2016. Innate Immune Responses to Tuberculosis. Microbiol Spectrum 4(6):TBTB2-0010-2016. doi:10.1128/microbiolspec.TBTB2-0010-2016.


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Tuberculosis remains one of the greatest threats to human health. The causative bacterium, , is acquired by the respiratory route. It is exquisitely adapted to humans and is a prototypic intracellular pathogen of macrophages, with alveolar macrophages being the primary conduit of infection and disease. However, bacilli interact with and are affected by several soluble and cellular components of the innate immune system which dictate the outcome of primary infection, most commonly a latently infected healthy human host, in whom the bacteria are held in check by the host immune response within the confines of tissue granuloma, the host histopathologic hallmark. Such individuals can develop active TB later in life with impairment in the immune system. In contrast, in a minority of infected individuals, the early host immune response fails to control bacterial growth, and progressive granulomatous disease develops, facilitating spread of the bacilli via infectious aerosols. The molecular details of the -host innate immune system interaction continue to be elucidated, particularly those occurring within the lung. However, it is clear that a number of complex processes are involved at the different stages of infection that may benefit either the bacterium or the host. In this article, we describe a contemporary view of the molecular events underlying the interaction between and a variety of cellular and soluble components and processes of the innate immune system.

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Schematic of the lung and the role of pulmonary innate immune cells during infection. From left to right: branching of the airways, culminating in the alveolar sacs and the alveolus. Also depicted are the cells in the alveolus. Abbreviations: AEC I and II, type I and II alveolar epithelial cell; AM, alveolar macrophage; DC, dendritic cell; IM, interstitial macrophage; IVM, intravascular macrophage.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.TBTB2-0010-2016
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Macrophage receptors known to engage () or its components and the downstream effects of receptor engagement on cytokine production, phagosome-lysosome fusion, and inflammation. Engagement of different receptors results in a macrophage response that can either promote or limit host immunity to infection.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.TBTB2-0010-2016
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() fate upon macrophage infection. Following phagocytosis, resides within a modified phagosome which may allow mycobacterial components to enter the cytosol in an ESX-1-dependent manner. The phagosome is also connected to the early endosomal network because membrane compartments can both fuse and bud from the phagosome, allowing exposure to important nutrients such as iron as well as removal of mycobacterial components. Endosomes containing mycobacterial components can fuse with multivesicular bodies (MVBs), leading to their incorporation into intraluminal vesicles, and upon MVB fusion with the plasma membrane, they can be released within exosomes (indicated as red circles in the figure). The phagosome has limited fusion with lysosomes, but with activation by IFN-γ or antibiotic treatment the -containing phagosome may undergo autophagosome formation and following lysosome fusion can limit growth, a process known as autophagy. There are also data suggesting that can escape into the cytosol, although this has been observed in only a limited number of studies.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.TBTB2-0010-2016
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Responses of innate immune cells to (), BCG, or their products, demonstrating both the beneficial and detrimental roles these cells have on controlling an infection.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.TBTB2-0010-2016
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