It is concluded that 4-1BB has the potential to be used as a biomarker to identify MAIT cells with enhanced IFN-γ and IL-17 responses that might be associated with tuberculosis infection control.
Since increased IL-17A levels are observed to be localized in the lung compartments (BAL and lymphocytes) in comparison to circulating levels, an inhalable PI3Kδ inhibitor, which is currently utilized for inflammatory airway diseases characterized by IL-17A over-secretion, may be a therapeutic option for active TB disease.
Overall, our findings demonstrated that the AA genotype from the IL-17Ars2275913 SNP is positively associated with protection to active tuberculosis but related to higher disease severity in the Argentinean population.
Therefore, ectopic lung B cell formation is important for containment of M. tuberculosis, and up-regulation of IL-17 and IL-22 responses may be an important mechanism underlying the protective role B cells in human tuberculosis.
IL17A augments autophagy in Mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease.
Our results suggest that the TT genotype of IL-17Ars3748067 might be a risk factor for TB in Asians; the A allele, as well as the AG and AA+AG genotypes of the rs2275913 polymorphism, might be protective against TB in Caucasians.
These findings strongly support the development of a NE-TB vaccine as a novel, safe and effective, first-of-kind IL-17 inducing mucosal vaccine for potential use in humans.
Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63<sub>lo</sub>) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.0-3.0 log reduction in CFU as compared to wild type BCG.
Our objective was to analyze, in an in vitro model, the influence of Infliximab on the granulomatous reactions and on the production of antigen-specific cytokines (TNF-α, IFN-γ, IL-12p40, IL-10 and IL-17) from beads sensitized with soluble Bacillus Calmette-Guérin (BCG) antigens cultured in the presence of peripheral blood mononuclear cells (PBMC) from TB patients.
The present findings deepen our understanding of the role of IL-17 in MDR-TB and highlight the influence of the genetic background of the infecting M. tuberculosis strain on the ex-vivo Th17 response.
In contrast, SNPs in the proinflammatory IL17A and IL17F genes (rs2275913 and rs763780, respectively), found previously to correlate with the disease occurrence in Chinese population, were not significantly associated with tuberculosis in the Croatian population.
Our studies highlight the potential value of targeting the IL-17-CXCL13 pathway rather than the IFNγ pathway as a new strategy to improve mucosal vaccines against TB.
Therefore, increased SOCS3 expression in human tuberculosis may reflect polarization toward IL-17-expressing T cells as well as T-cell exhaustion marked by reduced proliferation.
Our results show that TB(+)HIV(+) pleurisy results in significantly reduced frequency of CD4(+)IL-17(+)RORC(+)STAT3(+) Th17 cells compared to TB(-)HIV(-)ex vivo (p = 0.0054) and was confirmed in conditioned media studies in vitro (p = 0.0001).
Metabolites from anaerobic bacterial fermentation may, therefore, increase TB susceptibility by suppressing IFN-γ and IL-17A production during the cellular immune response to M. tuberculosis.
Accordingly, we examined the impact of individual versus combined neutralization of TNF-α and IL-17A in a mouse model of rheumatoid arthritis (collagen-induced arthritis) and the concomitant susceptibility to infections that are likely to manifest as side effects of blocking these cytokines (oral candidiasis or tuberculosis).