The PI3K-Akt-mTOR signaling pathway in T lymphocytes and CD4CD25FoxP3T cells was inhibited, which could explain why M.tuberculosis can induce FoxP3T cell to expand.

No abstract

The function of triggering receptor expressed on myeloid cell-like transcript 2 (TLT2) has not been characterized and their role in pulmonary tuberculosis (TB) remains unclear. In this study, we found that surface TLT2 was up-regulated in human monocytes of patients with active TB compared to healthy subjects. In vitro, TLT2 expression was induced in human monocyte cell line THP-1 cells after bacillus Calmette-Guérin (BCG) or Mycobacterium tuberculosis (Mtb) H37Rv infection. Knockdown of TLT2 by siRNA transfection suppressed IL-6 expression, whereas over-expression of TLT2 increased IL-6 production in THP-1 cells infected by H37Rv. TLT2 + CD14 + monocytes produced higher level of IL-6 compared to TLT2 − subset in active TB patients. Western blot and immunocoprecipitation revealed that TLT2 interacted with kinase JAK1/JAK2/Tyk2 to enhance STAT3 phosphorylation. Moreover, we showed that tyrosine residues 297 and 315 of TLT2 cytoplasmic domain were involved in STAT3 activation. In monocyte/CD4 + T cell co-culture assay, blockage of TLT2 fusion protein facilitated IFN-γ production by CD4 + T cells. Plate count assay showed that monocyte-mediated bacterial killing was promoted by TLT2 fusion protein. In vivo treatment with TLT-2 fusion protein reduced IL-6 production by macrophage but increased IFN-γ production by CD4 + T cell in H37Rv and BCG infected mice. Furthermore, TLT2 fusion protein attenuated inflammation, and reduced bacterial load in lung of infected mice. Together, these findings demonstrate that TLT2 negatively regulates Th1 response against mycobacterial infection, which promotes IL-6 production through JAK/STAT3 signal pathway.

A total of 1,271 persons living in a socially and economically depressed, inner-city area of Vancouver, British Columbia, voluntarily attended a tuberculosis case-finding campaign. Chest x-ray, on-the-spot specimen of sputum, and tuberculin skin test were offered at the time of the first attendance. All 3 diagnostic methods were found to be well accepted, with 93% of the participants having an x-ray, over 95% producing a sputum specimen, and almost 95% having a tuberculin test (a quarter of these did not, however, report for reading of the test). Eight cases of bacteriologically confirmed pulmonary tuberculosis were found: 6 suspected on x-ray (the remaining 2 films were abnormal but not diagnostic of tuberculosis), and 6 being positive on smear and/or culture of the initial on-the-spot sputum specimen. Examination of a second specimen of sputum diagnosed all of the 8 active cases identified by the survey. These results suggest that, in this particular setting, a chest radiogram taken by a transportable chest x-ray apparatus or examination of 2 sputum specimens might be equally successful at detecting all cases of active pulmonary tuberculosis within the time required for sputum culture. Examination of the sputum smear immediately identifies all the more infectious cases of pulmonary tuberculosis. The prevalence rate of 629 per 100,000 among those presenting themselves to this campaign illustrates the high-yield which might be achieved by active case-finding projects in known high-incidence segments of a generally low-incidence population.