Dendritic Cells in Host Immunity to Mycobacterium tuberculosis

Marc Mendelson; Gilla Kaplan; Willem Hanekom

doi:10.1128/9781555817657.ch28

Chapter 28 : Dendritic Cells in Host Immunity to Mycobacterium tuberculosis

Authors: Marc Mendelson¹, Gilla Kaplan¹, Willem Hanekom²

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Affiliations: 1: Laboratory of Mycobacterial Immunity and Pathogenesis, Public Health Research Institute, International Center for Public Health, Newark, NJ 07103; 2: Departments of Pediatrics and of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 33136

Content Type: Monograph

Publication Year: 2005

Category: Bacterial Pathogenesis; Clinical Microbiology

Book DOI: 10.1128/9781555817657

Chapter DOI: 10.1128/9781555817657.ch28

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Abstract:

Since their identification by Steinman and Cohn over 30 years ago, dendritic cells (DCs) have been shown to play a central role in the initiation and control of the protective host immune response to pathogens. Recent advances in the understanding of the interactions between DCs and Mycobacterium tuberculosis and how these interactions affect the course of immune activation and induction of protection against infection are reviewed. Phagocytosis of particulate material and intact organisms occurs by receptor-mediated endocytosis. Engagement of costimulatory molecules by CD28 expressed on the surface of the T cells leads to recruitment of membrane rafts containing kinases and adapters to the immunological synapse, thus amplifying by up to 100-fold the signaling process started by T-cell receptor engagement. The importance of this cytokine in regulating the immune response is highlighted by the observation that individuals with germ line mutations in genes of the interleukin-12 (IL-12) receptor and signaling pathway (that result in defective activity) have an increased risk of contracting mycobacterial diseases, including tuberculosis. Despite increasing knowledge about the interaction between M. tuberculosis and DCs in vitro, relatively little is known about the sequence of events during infection with M. tuberculosis in vivo. Researchers have recently initiated studies to compare the number and function of blood DCs in human immunodeficiency virus-seronegative adults with various clinical presentations of tuberculosis (TB).

Citation: Mendelson M, Kaplan G, Hanekom W. 2005. Dendritic Cells in Host Immunity to Mycobacterium tuberculosis, p 451-462. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch28

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Immune Systems: 0.46989053
Tumor Necrosis Factor alpha: 0.44691974
Plasmacytoid Dendritic Cells: 0.44001734
Major Histocompatibility Complex: 0.43570125

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Dendritic Cells in Host Immunity to Mycobacterium tuberculosis

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Figure 1

(A) Electron micrograph of an in vitro-matured monocyte- derived DC showing the characteristic dendritic processes (arrows). (B) Monocyte-derived DC infected with M. tuberculosis (arrow), with a higher-magnification view (insert) showing replicating M. tuberculosis bacilli (arrows).

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Figure 1

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Figure 2

The outcome of infection of DCs by M. tuberculosis may depend on the capacity of the infecting strain to induce DC maturation. In the figure, infection with strain A induces suboptimal DC maturation, thereby inducing a weak Th1 response. The immature state of the infected DC augments the action of Tr cells, allowing active disease and subsequent persistence. Strain B, in contrast, induces optimal DC maturation and a strong Th1 response, leading to control of the infection and reducing the chance of active disease.

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Figure 2

References

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