Modulation of Cell Death byM. tuberculosisas a Strategy for Pathogen Survival

Abstract

It has been clearly demonstrated thatin vitro, virulentM. tuberculosiscan favor necrosis over apoptosis in infected macrophages, and this has been suggested as a mechanism for evading the host immune response. We recently reported that an effect consistent with this hypothesis could be observed in cells from the blood of TB patients, and in this paper, we review what is known about evasion strategies employed byM. tuberculosisand in particular consider the possible interaction of the apoptosis-inhibiting effects ofM. tuberculosisinfection with another factor (IL-4) whose expression is thought to play a role in the failure to controlM. tuberculosisinfection. It has been noted that IL-4 may exacerbate TNF-α-induced pathology, though the mechanism remains unexplained. Since pathology in TB typically involves inflammatory aggregates around infected cells, where TNF-α plays an important role, we predicted that IL-4 would inhibit the ability of cells to removeM. tuberculosisby apoptosis of infected cells, through the extrinsic pathway, which is activated by TNF-α. Infection of human monocytic cells with mycobacteriain vitro, in the presence of IL-4, appears to promote necrosis over apoptosis in infected cells—a finding consistent with its suggested role as a factor in pathology duringM. tuberculosisinfection.