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

Abstract

Identification of Mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for TB. Levels of IFN-γ, IL-2, IL-17, IL-10, IP-10 and MIP-1α 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(+)TB(+)), HIV negative TB patients (HIV(-)TB(+)), HIV positive tuberculin skin test positive (TST+) (HIV(+)TST(+)), HIV negative TST+ (HIV(-)TST(+)), and HIV(-)TST(-) individuals. Compared to HIV(-)TST(-), latent TB infection led to increased levels of IP-10, IFN-γ and IL-17, while levels of IL-2 and IP-10 were increased with active TB. Levels of IFN-γ, IL-17, MIP-1α, and IL-10 were increased in HIV(-)TST(+) individuals compared to HIV(-)TB(+) patients. HIV coinfection decreased the level of IFN-γ, IL-17, IP-10 and IL-2. After six months (M6) of anti-TB treatment (ATT) in HIV(-)TB(+) patients, IFN-γ, IL-10, and MIP-1α levels normalized. After M6 and M18 of ATT plus HAART in HIV(+)TB(+) patients, levels of MIP-1α and IL-10 normalized, while this was not the case for IFN-γ, IL-2, IL-17, and IP-10 levels. In HIV(+)TST(+) patients on HAART, levels of IFN-γ, IL-17, IL-10 and MIP-1α normalized, while no change in the levels of IL-2 and IP-10 were observed. In conclusion, the simultaneous measurement of IFN-γ, IL-17 and IP-10 may assist in diagnosing LTBI; IL-2 and IP-10 may assist in diagnosing active TB; while IFN-γ, IL-17, MIP-1α, and IL-10 levels could help to discriminate LTBI and active TB. In addition, IL-10 and MIP-1α levels could help to monitor responses to TB treatment and HAART.

IFN-γ, IL-2, IP-10, and MIG as Biomarkers of Exposure to Leishmania spp., and of Cure in Human Visceral Leishmaniasis

“…Cell-mediated immunity tests have recently been proposed for the follow-up of patients co-infected with HIV/ Leishmania (Castro et al, 2016). Since IP-10 identifies HIV/tuberculosis-infected patients, despite their low CD4 counts (Azzurri et al, 2005; Kassa et al, 2016), it might be used to monitor for relapses of leishmaniasis in HIV/ Leishmania -infected patients.…”

Malnutrition: Modulator of Immune Responses in Tuberculosis

“…Individuals with low BMI have diminished circulating levels of proinflammatory (IFN-γ, TNF-α, IL-22, IL-1α, IL-1β, and IL-6) cytokines but elevated levels of regulatory cytokines (IL-10, TGF-β, IL-5, IL-13) ( 52 ). This group demonstrated a positive correlation between the circulating levels of pro-inflammatory cytokines and high BMI (between 25 and 29.9) and a negative correlation between the circulating levels of anti-inflammatory cytokines and low BMI ( 53 , 54 ). These data suggest a protective mechanism of BMI against progression of TB infection to disease by altering the cytokine milieu of an individual.…”

Associations between systemic inflammation, mycobacterial loads in sputum and radiological improvement after treatment initiation in pulmonary TB patients from Brazil: a prospective cohort study

“…The determinants of the TB clinical presentation are described to involve a complex relationship between the mycobacterium and the host immune responses [ 2 , 3 ]. Successful host response against M. tuberculosis requires the production of pro-inflammatory cytokines including IFN-γ and TNF-α [ 4 , 5 ]. Indeed, individuals genetically deficient in molecules from the IFN pathway, as well as those under treatment of chronic conditions with TNF-α blockers, are highly susceptible to severe TB [ 6 ].…”