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2017 ; 8
(ä): 294
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Interactions between Type 1 Interferons and the Th17 Response in Tuberculosis:
Lessons Learned from Autoimmune Diseases
#MMPMID28424682
Mourik BC
; Lubberts E
; de Steenwinkel JEM
; Ottenhoff THM
; Leenen PJM
Front Immunol
2017[]; 8
(ä): 294
PMID28424682
show ga
The classical paradigm of tuberculosis (TB) immunity, with a central protective
role for Th1 responses and IFN-?-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-?
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-CSF-secreting 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.