Journal
FRONTIERS IN IMMUNOLOGY
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2017.00294
Keywords
Mycobacterium tuberculosis; autoimmune diseases; neutrophils; inflammation; tertiary lymphoid structures; antibodies; B-cell-activating factor
Categories
Funding
- EC FP7 ADITEC [280873]
- EC HORIZON TBVAC [643381]
- EC FP7 EURIPRED (FP7-INFRA) [312661]
- Netherlands Organization for Scientific Research (NWO-TOP) [91214038]
- Bill & Melinda Gates Foundation Grand Challenges in Global Health [GC6-2013]
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R21AI127133]
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The classical paradigm of tuberculosis (TB) immunity, with a central protective role for Th1 responses and IFN-gamma-stimulated cellular responses, has been challenged by unsatisfactory results of vaccine strategies aimed at enhancing Th1 immunity. Moreover, preclinical TB models have shown that increasing IFN-gamma responses in the lungs is more damaging to the host than to the pathogen. Type 1 interferon signaling and altered Th17 responses have also been associated with active TB, but their functional roles in TB pathogenesis remain to be established. These two host responses have been studied in more detail in autoimmune diseases (AID) and show functional interactions that are of potential interest in TB immunity. In this review, we first identify the role of type 1 interferons and Th17 immunity in TB, followed by an overview of interactions between these responses observed in systemic AID. We discuss (i) the effects of GM-CSFsecreting Th17.1 cells and type 1 interferons on CCR2(+) monocytes; (ii) convergence of IL-17 and type 1 interferon signaling on stimulating B-cell activating factor production and the central role of neutrophils in this process; and (iii) synergy between IL-17 and type 1 interferons in the generation and function of tertiary lymphoid structures and the associated follicular helper T-cell responses. Evaluation of these autoimmune-related pathways in TB pathogenesis provides a new perspective on recent developments in TB research.
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