Effective control of tuberculosis (TB) includes discrimination of subjects with active TB from individuals with latent TB infection (LTBI). As distinct interferon (IFN)-gamma and interleukin (IL)-2 profiles of antigen-specific T-cells have been associated with different clinical stages and antigen loads in several viral and bacterial diseases, we analysed these cytokines in TB using a modified QuantiFERON-TB Gold In Tube test. Detection of IL-2 in addition to IFN-gamma distinguishes not only Mycobacterium tuberculosis-infected subjects from healthy controls, but also individuals with LTBI from active TB patients. This may help to improve diagnostic tests for TB.

Oleanolic acid is a triterpenoid which is quite common in nature in the form either of free acid or in triterpenoid saponin glycosides. This study describes the effect of oleanolic acid on the growth of human immunodeficiency virus-1 (HIV-1) in cultures of human peripheral mononuclear cells (PBMC) and of monocyte/macrophages (M/M). Its inhibitory activity was also evaluated on PBMC obtained from HIV-1 infected patients. Results obtained show that oleanolic acid inhibits the HIV-1 replication in all the cellular systems used (EC50 values: 22.7 microM, 24.6 microM and 57.4 microM for in vitro infected PBMC, naturally infected PBMC and M/M, respectively). As regards the mechanism of action, oleanolic acid inhibits in vitro the HIV-1 protease activity.

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SummaryDendritic cells (DC) have been characterized recently as having an important role in the initiation and control of immunological response to Mycobacterium tuberculosis infection. Blood DC have been subdivided into myeloid (mDC) and plasmacytoid (pDC) subsets, on the basis of differences in phenotype markers and function. Little is known about the enumeration and functional evaluation of circulating DC in patients with tuberculosis and their correlation with clinical outcome during the course of anti-tuberculous treatment. We assessed circulating mDC and pDC counts measured by a newly developed single-platform flow cytometric assay based on TruCOUNT, as well as the production of interferon (IFN)-α α α α after in vitro stimulation by herpes simplex virus (HSV-1) in 24 patients with active tuberculosis (TB) and 37 healthy donors. Absolute numbers of both DC subsets were decreased significantly in patients with active TB compared to controls. Similarly, the production of IFN-α α α α was highly impaired. In 13 patients these parameters were assessed longitudinally, before and after the specific anti-microbial treatment. Most interestingly, in all nine patients with successful anti-tuberculous therapy there was a significant and marked increase of pDC counts and IFN-α α α α production. In contrast, no significant longitudinal variations in DC counts and IFN-α α α α production were observed in four patients with lack of response to specific treatment. In conclusion, active TB is associated with a defect in blood DC numbers and IFN-α α α α production that is restored after bacterial clearance and clinical improvement, as a result of effective anti-tuberculous treatment.

The functional improvement of two critical components of innate antimicrobial immunity, such as neutrophils and monocytes, may contribute to the improved cell-mediated immune responses against opportunistic infections in HAART-treated patients.