By analyzing the cellular responses to mycobacterial antigens in patients who had latent tuberculosis with or without filarial infection, we were able to demonstrate that filarial infection coincident with M. tuberculosis infection significantly diminishes M. tuberculosis-specific Th1 (interleukin [IL]-12 and IFN-gamma) and type 17 T helper (Th17; IL-23 and IL-17) responses related to increased expression of cytotoxic T lymphocyte antigen (CTLA)-4 and programmed death (PD)-1.
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.
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 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.
To date, only one study performed in Chinese Han population has found an association between IL-17F sequence variants and susceptibility to tuberculosis, but no relationship has been found with another single nucleotide polymorphism (SNP) in IL-17A gene (rs2275913).
These findings demonstrate that increased PD-1 expression and decreased pSTAT3 expression reduce IL-23 receptor expression and IL-17 production by CD4(+) T cells of tuberculosis patients.
All mice showed strong antibody responses to the InsB protein, and splenocytes stimulated with InsB showed strong IFN-γ and IL-17 responses and a weak IL-2 response, all of which have been implicated in disease expression and used for the immunodiagnosis of TB.
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.
In addition, studies on the human macrophage methylation profiles from the patient cohorts indicated that the methylation rate of IL17 family members and related genes were significantly altered in patients with active MTB infections.
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).
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.
The expression of IL-17 and IL-10 was significantly increased in active TB patients in comparison to that in latent TB or control groups (IL-17: 16.85±9.68 vs. 7.23±5.19 or 8.21±5.51pg/mL, p<0.05; IL-10: 28.70±11.27 vs. 20.25±8.57 or 13.94±9.00pg/mL, p<0.05).
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.
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.
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.
IL17A augments autophagy in Mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease.
Mucosal T-helper cells producing IFN-γ (Th1) and IL-17 (Th17) are important for protecting against tuberculosis (TB), but the mechanisms by which DCs generate antigen-specific T-helper responses during Mtb infection are not well defined.
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.