Chapter 27 : Intracellular Models of Infection

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Intracellular models of infection have proven to be invaluable tools to address diverse questions in mycobacterial research. This chapter begins with an analysis of basic host-pathogen interactions in the infected murine macrophage. It then describes two models in which infected human monocytes interact with lymphocytes and other cells to generate antimycobacterial activity. Lastly, the chapter summarizes clinical trials in which these models were used to analyze the effects of BCG vaccination and other immunologic interventions. The best-studied macrophage antimycobacterial mechanisms are those mediated by (i) the production of nitric oxide (NO) and related reactive nitrogen intermediates (RNI) and (ii) phagolysosomal fusion. Recent microarray analyses have demonstrated that RNI can regulate gene expression in vitro. It is becoming clear that can interfere with the tethering and fusion machinery involved in phagolysosomal biogenesis. Natural killer (NK) cells have the capacity to kill intracellular , whether these cells are isolated from PPD-positive or PPD-negative subjects. The ability of tuberculin reactors to control growth could be blocked by antibodies to gamma interferon (IFN-γ) or tumor necrosis factor (TNF-α) and could be inhibited by methylprednisolone or pentoxifylline. Impaired control of infection was not reconstituted by the addition of exogenous IFN-γ but, in a small cohort, improved following initiation of antiretroviral therapy.

Citation: Chan J, Silver R, Kampmann B, Wallis R. 2005. Intracellular Models of Infection, p 437-450. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch27
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Figure 1

After phagocytosis, the tubercle bacillus is subject to attack by reactive radicals including various reactive nitrogen intermediates (RNI) and the hydrolytic enzymes of the lysosome. has evolved sophisticated means by which these potent antimicrobial activities of macrophages can be evaded.

Citation: Chan J, Silver R, Kampmann B, Wallis R. 2005. Intracellular Models of Infection, p 437-450. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch27
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Table 1

Immune control of mycobacterial growth in the blood of tuberculosis patients and healthy volunteers

Citation: Chan J, Silver R, Kampmann B, Wallis R. 2005. Intracellular Models of Infection, p 437-450. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch27

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