The effect of HIV coinfection, HAART and TB treatment on cytokine/chemokine responses to Mycobacterium tuberculosis (Mtb) antigens in active TB patients and latently Mtb infected individuals

summary Identification of Mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for TB. Levels of IFN-g, IL-2, IL-17, IL-10, IP-10 and MIP-1a were measured in supernatants of whole blood stimulated with Mtb specific fusion protein ESAT-6/CFP-10 using xMAP technology. The study groups were HIV positive TB patients (HIV þ TB þ ), HIV negative TB patients (HIVTB þ ), HIV positive tuberculin skin test positive (TSTþ) (HIV þ TST þ ), HIV negative TSTþ (HIVTST þ ), and HIVTSTindividuals. Compared to HIVTST � , latent TB infection led to increased levels of IP-10, IFN-g and IL-17, while levels of IL-2 and IP-10 were increased with active TB. Levels of IFN-g, IL-17, MIP-1a, and IL-10 were increased in HIVTST þ individuals compared to HIVTB þ patients. HIV coinfection decreased the level of IFN-g, IL- 17, IP-10 and IL-2. After six months (M6) of anti-TB treatment (ATT) in HIVTB þ patients, IFN-g, IL-10, and MIP-1a levels normalized. After M6 and M18 of ATT plus HAART in HIV þ TB þ patients, levels of MIP-1a and IL-10 normalized, while this was not the case for IFN-g, IL-2, IL-17, and IP-10 levels. In HIV þ TST þ patients on HAART, levels of IFN-g, IL-17, IL-10 and MIP-1a normalized, while no change in the levels of IL-2 and IP-10 were observed. In conclusion, the simultaneous measurement of IFN-g, IL-17 and IP-10 may assist in diagnosing LTBI; IL-2 and IP-10 may assist in diagnosing active TB; while IFN-g, IL-17, MIP-1a, and IL-10 levels could help to discriminate LTBI and active TB. In addition, IL-10 and MIP-1a levels could help to monitor responses to TB treatment and HAART.