M. tuberculosis infection and antigen specific cytokine response in healthcare workers frequently exposed to tuberculosis

Abstract Tuberculosis (TB) is the leading cause of death due to an infectious agent, but only a small fraction of those infected develop the disease. Cytokines are involved in the mediation and regulation of immunity, and their secretion patterns may reflect the infection status. To increase our understanding of immune response toM.tuberculosisinfection, we conducted a cross-sectional study investigatingM.tuberculosisinfection status and comparing the release profiles of cytokines GM-CSF, IFN-γ, IL-1β, IL-10, IL-12 (p70), IL-2, IL-4, IL-5, IL-6, IL-8, TNF-α, in community controls (CCs) and healthy healthcare workers (HCWs) highly exposed to TB. Among HCWs and CCs, the probability of latentM.tuberculosis(LTB+) infection was respectively 5.4 (p = 0.002) and 3.4 (p = 0.006) times higher in men than women. The odds ratio of LTB infection was 4 times higher among HCWs in direct contact with active TB patients than other HCW (p = 0.01). Whole blood supernatant cytokine responses toM.tuberculosisantigens showed differential pro-inflammatory responses between HCWs and CCs. CCsLTB−had higher IL-1β responses than HCWsLTB−(p = 0.002). HCWsLTB+had significantly higher IL-8 responses toM.tuberculosisantigens than HCWsLTB−(p = 0.003) and CCsLTB−(p = 0.015). HCWsLTB+/−showed weak but positive TNF-α responses toM.tuberculosisantigen stimulation compared to CCsLTB+/−(p ≤ 0.015). Looking at T-helper (1 and 2) responses, HCWsLTB+and CCsLTB+had significantly higher IFN-γ and IL-2 responses compared to HCWsLTB−and CCsLTB−(p < [0.0001–0.003]). Also, TB antigen induced IL-5 secretion was significantly higher in HCWsLTB+and CCsLTB+than in non-infected CCsLTB−(p < [0.005–0.04]).M.tuberculosisantigen specific responses in HCWsLTB+varied based on active TB exposure gradient. HCWsLTB+who were highly exposed to active TB (≥3 hours per day) had significantly higher IFN-γ and IL-8 responses (p ≤ 0.02) than HCWsLTB+not in direct contact with active TB patients. HCWsLTB+working with active TB patients for 5 to 31 years had a significantly enhanced secretion of proinflammatory cytokines (GM-CSF, IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-12p70, TNF-α) compared to HCWsLTB−(p < [0.0001–0.01]). Secretion of anti-inflammatory/Th2 cytokines IL-5 and IL-10 was also higher in HCWsLTB+than HCWsLTB−. In conclusion, LTBI individuals controlling theM.tuberculosisinfection have an enhanced TB specific Th1-cytokines/proinflammatory response combined with selected Th2 type/anti-inflammatory cytokines induction.