Abstract
While homeostatic apoptosis is immunologically silent, macrophage apoptosis during Mycobacterium tuberculosis infection can potentially induce an immune response against the mycobacteria. To examine the role of dendritic cells in this response, macrophage apoptosis was induced by incubating the macrophage with cell wall extracts of mycobacteria expressing LpqH. The apoptogenic proteins of the cell wall extracts were engulfed by the macrophage and then were translocated from the cytosol to the nuclei of the dying cells. Dendritic cells that engulfed the apoptotic macrophages acquired an immunogenic phenotype that included upregulation of MHC-I, increased expression of the costimulatory molecules, CD40, CD80, and CD86, and increased production of IL-12, IL-10, TNF-α, and TGF-β. In addition, the dendritic cells triggered a proliferative response of CD8+ T cells with IFN-γ production via cross-presentation. Taken together, these findings support a model in which phagocytosis of whole apoptotic cells carrying mycobacterial antigens promotes a potentially protective immune response.
Highlights
An immune response against Mycobacterium tuberculosis (Mtb) involves both innate and adaptive immune mechanisms [1]
Dendritic cells (DCs) that engulf apoptotic blebs acquire the ability to trigger an immune response of T cells. It is unknown if the apoptotic bodies that remain after the release of blebs are immunogenic [17]. This is relevant because it has been reported that blebs and apoptotic bodies differ in their effects on immunity in order to gain a better understanding of the role played by host cell apoptosis in antimycobacterial immunity, we studied the maturation profile, autocrine cytokine production and the T cell response elicited by bone marrow-derived DCs that phagocytosed whole apoptotic MØs carrying mycobacterial proteins [18]
We found that DCs that engulfed apoptotic MØ carrying mycobacterial antigens developed a maturation profile that triggered the proliferation of CD8 T cells and IFN-γ production
Summary
An immune response against Mycobacterium tuberculosis (Mtb) involves both innate and adaptive immune mechanisms [1]. Dendritic cells (DCs) that are located near the alveoli can capture incoming bacilli, and travel to the hilar lymph nodes to process and present antigens to T cells [2]. An adaptive immune T cell response is initiated and mediated by CD4 and CD8 cells [1]. A number of observations support the view that apoptosis of macrophages (MØ) infected by Mtb constitutes an innate immune response [3] Currently, there is much interest in this response since it has been well established that homeostatic apoptosis regulates tissue turnover in the body to maintain stable cell populations, yet this process is not immunogenic [4].
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