Pulmonary mucosal dendritic cells in T-cell activation: implications for TB therapy

Abstract

Mycobacterium tuberculosis, the causative agent of pulmonary TB, causes chronic intracellular infection of lung-resident antigen-presenting cells, including macrophages and dendritic cells (DCs). Life-long bacterial control requires robust T-cell immune responses. Lung DCs are critical for initiating and co-ordinating adaptive immune responses against TB. The recent description of previously uncharacterized DC subsets has prompted the re-examination of lung DCs and their role in priming antimycobacterial T-cell responses. While there is some data on these new DCs in their naive state, very little is known about how these DCs respond to pulmonary mycobacterial infection. In this article, we attempt to identify the major antigen-presenting cell subsets that may be critical to lymph node homing, T-cell priming and controlling mycobacterial infection. We further examine the areas of DC heterogeneity that may relate to differential susceptibility between mouse strains. Furthermore, we discuss how DCs may be manipulated and exploited as a cell-based prophylactic TB vaccine and the prospect of using this strategy for post-M. tuberculosis exposure settings.

Keywords::

• alveolar macrophages
• DC vaccines
• dendritic cells
• ex vivo manipulated DC
• lung
• migration
• Mycobacterium tuberculosis
• T cells
• tuberculosis

Financial & competing interests disclosure

The authors’ work cited in this contribution is supported by funds from the Canadian Institutes for Health Research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.