Apoptosis of Human Monocytes/Macrophages Inmycobacterium Tuberculosis Infection

Abstract

Tuberculosis (TB) is still a major health problem, both as a single disease entity and as a cofactor in AIDS. The interaction between macrophage and Mycobacterium tuberculosis (MTB) is a critical step in the establishment of an early chronic infection. This study analyses the capacity of MTB to induce apoptosis in cells obtained by broncho‐alveolar lavage (BAL) from patients with reactive pulmonary tuberculosis and from AIDS patients with disseminated pulmonary tuberculosis. Apoptosis was increased three‐fold in BAL cells obtained from patients with pulmonary tuberculosis and even more markedly in alveolar macrophages of MTB‐infected AIDS patients, compared with controls. Apoptosis was analysed and characterized by propidium iodide (PI) incorporation, terminal deoxy transferase (TDT)‐mediated dUTP‐biotin nick end labelling (TUNEL), and tissue transglutaminase (tTG) expression. The MTB–macrophage interaction was also investigated in vitro by infecting monocyte‐derived macrophages (MDM) with MTB (virulent strain H37Rv). The induction of apoptosis by MTB required viable bacteria, was dose‐dependent, and was restricted to H37Rv. Infection with either Mycobacterium avium complex (MAC) or HIV‐1 and treatment with heat‐killed MTB failed to induce apoptosis. © 1997 by John Wiley & Sons, Ltd.

Expression, production and release of the Eis protein by Mycobacterium tuberculosis during infection of macrophages and its effect on cytokine secretion

“…The induction of downregulatory cytokines, such as IL-10 and transforming growth factor-b, can inhibit interferon (IFN)-c production by T cells and block or inhibit macrophage activation and apoptosis (Flesch et al, 1994;Othieno et al, 1999). It is widely known that in alveolar macrophages, apoptosis is a common defence mechanism against M. tuberculosis infection via a TNF-a-mediated pathway (Placido et al, 1997). Monocytes from patients with active TB when compared to those from healthy donors are not only likely to secrete more IL-10 than TNF-a in response to stimulation with PPD, but they are also more likely to undergo necrosis than apoptosis (Gil et al, 2004).…”

“…These cytokines are known to play a significant role in the pro-and antiinflammatory components respectively of the immune response to M. tuberculosis infection (Flynn et al, 1995;Gong et al, 1996). Mycobacterial proteins/lipids released from the phagosome of M. tuberculosis-infected macrophages have also been shown to modulate levels of cytokine secretion during infection, to the advantage of the pathogen (Gil et al, 2004;Placido et al, 1997;Rivera-Marrero et al, 2004).…”

The role of macrophage cell death in tuberculosis

“…These data indicate that M. tuberculosis challenge in some way sensitizes AMF to autocrine and/or paracrine TNFa-mediated apoptosis. Apoptosis of primary human monocyte-derived macrophages (MDMF) following exposure of M. tuberculosis H37Rv in vitro was reported by Placido et al, 23 and Klingler et al 24 noted a similar response to H37Ra. The data of Placido and Keane both indicate that apoptosis requires challenge with live mycobacteria; heat-killed organisms had no effect on macrophage viability.…”

MEF2C mediates the activation induced cell death (AICD) of macrophages

“…Apoptosis of immune cells including macrophages has been found to occur in inflammatory diseases [1][2][3][4][5]. Apoptosis of activated macrophages may serve to restrict and focus the immune response, but it may also reduce the host defenses against infectious pathogens or contribute to immune suppression.…”

“…It has been suggested that the lifespan of macrophages in inflammation sites was extended by survival factors such as apoptosis inhibitor and nerve growth factor secreted by macrophages or other cells [9,10]. On the other hand, macrophage death has been observed in many inflammatory diseases [1][2][3][4][5]. Macrophage death could result from different causes.…”