Publisher Correction: M. tuberculosis infection and antigen specific cytokine response in healthcare workers frequently exposed to tuberculosis (original) (raw)
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Scientific Reports
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 to M. tuberculosis infection, we conducted a cross-sectional study investigating M. tuberculosis infection 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 latent M. 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 to M. tuberculosis antigens showed differential pro-inflammatory responses between HCWs and CCs. CCs LTB− had higher IL-1β responses than HCWs LTB− (p = 0.002). HCWs LTB+ had significantly higher IL-8 responses to M. tuberculosis antigens than HCWs LTB− (p = 0.003) and CCs LTB− (p = 0.015). HCWs LTB+/− showed weak but positive TNF-α responses to M. tuberculosis antigen stimulation compared to CCs LTB+/− (p ≤ 0.015). Looking at T-helper (1 and 2) responses, HCWs LTB+ and CCs LTB+ had significantly higher IFN-γ and IL-2 responses compared to HCWs LTB− and CCs LTB− (p < [0.0001-0.003]). Also, TB antigen induced IL-5 secretion was significantly higher in HCWs LTB+ and CCs LTB+ than in non-infected CCs LTB− (p < [0.005-0.04]). M. tuberculosis antigen specific responses in HCWs LTB+ varied based on active TB exposure gradient. HCWs LTB+ who were highly exposed to active TB (≥3 hours per day) had significantly higher IFN-γ and IL-8 responses (p ≤ 0.02) than HCWs LTB+ not in direct contact with active TB patients. HCWs LTB+ 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 HCWs LTB− (p < [0.0001-0.01]). Secretion of antiinflammatory/Th2 cytokines IL-5 and IL-10 was also higher in HCWs LTB+ than HCWs LTB−. In conclusion, LTBI individuals controlling the M. tuberculosis infection have an enhanced TB specific Th1-cytokines/ proinflammatory response combined with selected Th2 type/anti-inflammatory cytokines induction.
Serum concentrations of cytokines in patients with active tuberculosis (TB) and after treatment
Clinical and Experimental Immunology, 1999
During TB cytokines play a role in host defence. To determine the cytokine pattern during various disease stages of TB, serum levels of IL-12, interferon-gamma (IFN-g), IL-4, IL-6 and IL-10 were measured in 81 patients with active TB, 15 patients during therapy and 26 patients after anti-tuberculous therapy as well as in 16 persons who had been in close contact with smear-positive TB and in 17 healthy controls. IFN-g was elevated during active TB when compared with healthy controls, declining during and after treatment. IL-12 (p40 and p70) serum levels were not signi®cantly higher in patients with active TB compared with any of the other groups. IL-4 levels were low in all groups. IL-6 and IL-10 serum levels were elevated in patients with active TB and during treatment. In patients with active TB serum levels of IFN-g and IL-6 were higher in patients with fever, anorexia and malaise. IL-12 levels were higher in patients with a positive smear. Cytokine levels did not correlate with localization of TB (pulmonary versus extrapulmonary), or skin test positivity. Cytokines directing a Th1 response (IL-12) or a Th2 response (IL-4) were not elevated in sera of this large group of patients with pulmonary and extrapulmonary TB. In patients with active TB, cytokines that were elevated in serum were IFN-g, IL-6 and IL-10.
Health care workers’ immune profiles associated with development of active tuberculosis
Current Infectious Disease Reports
We evaluated immune responses to Mycobacterium tuberculosis in 10 health-care workers (HCWs) and 10 non-HCWs and correlated their immune status with the development of active tuberculosis (TB). Twenty individuals were randomly recruited, tested, and monitored longitudinally for TB presentation. Peripheral blood mononuclear cells (PBMCs) from donors were stimulated with M. tuberculosis and tested for cell proliferation and the production of interferon (IFN)-g, interleukin (IL)-5, and IL-4, by use of enzyme-linked immunosorbent or flow-cytometric assays. HCWs had higher levels of cell proliferation (24,258 cpm) and IFN-g (6373 pg/mL) to M. tuberculosis than did non-HCWs (cell proliferation, 11,462 cpm; IFN-g, 3228 pg/ mL). Six of 10 HCWs showed increased median percentages of CD8 + IL-4 + (4.7%) and gd + IL-4 + (2.3%) T cells and progressed to active TB. HCWs who remained healthy showed increased median percentages of CD8 + IFNg + (25.0%) and gd + IFN-g + (8.0%) and lower percentages of CD8 + IL-4 + (0.05%) and gd + IL-4 + (0.03%) T cells.
Gamma delta T cell responses associated with the development of tuberculosis in health care workers
2005
This study evaluated T cell immune responses to purified protein derivative (PPD) and Mycobacterium tuberculosis (Mtb) in health care workers who remained free of active tuberculosis (HCWs w/o TB), health care workers who went on to develop active TB (HCWs w/TB), non-health care workers who were TB free (Non-HCWs) and tuberculosis patients presenting with minimal (Min TB) or advanced (Adv TB) disease. Peripheral blood mononuclear cells (PBMC) were stimulated with Mtb and PPD and the expression of T cell activation markers CD25+ and HLA-DR+, intracellular IL-4 and IFN-c production and cytotoxic responses were evaluated. PBMC from HCWs who developed TB showed decreased percentages of cells expressing CD8+CD25+ in comparison to HCWs who remained healthy. HCWs who developed TB showed increased cd TCR+ cell cytotoxicity and decreased CD3+cd TCRÀ cell cytotoxicity in comparison to HCWs who remained healthy. PBMC from TB patients with advanced disease showed decreased percentages of CD25+CD4+ and CD25+CD8+ T cells that were associated with increased IL-4 production in CD8+ and cd TCR+ phenotypes, in comparison with TB patients presenting minimal disease. TB patients with advanced disease showed increased cd TCR+ cytotoxicity and reduced CD3+cd TCRÀ cell cytotoxicity. Our results suggest that HCWs who developed TB show an early compensatory mechanism involving an increase in lytic responses of cd TCR+ cells which did not prevent TB.
Journal of Infectious Diseases, 2004
We evaluated immune responses to Mycobacterium tuberculosis in 10 health-care workers (HCWs) and 10 non-HCWs and correlated their immune status with the development of active tuberculosis (TB). Twenty individuals were randomly recruited, tested, and monitored longitudinally for TB presentation. Peripheral blood mononuclear cells (PBMCs) from donors were stimulated with M. tuberculosis and tested for cell proliferation and the production of interferon (IFN)-g, interleukin (IL)-5, and IL-4, by use of enzyme-linked immunosorbent or flow-cytometric assays. HCWs had higher levels of cell proliferation (24,258 cpm) and IFN-g (6373 pg/mL) to M. tuberculosis than did non-HCWs (cell proliferation, 11,462 cpm; IFN-g, 3228 pg/ mL). Six of 10 HCWs showed increased median percentages of CD8 + IL-4 + (4.7%) and gd + IL-4 + (2.3%) T cells and progressed to active TB. HCWs who remained healthy showed increased median percentages of CD8 + IFNg + (25.0%) and gd + IFN-g + (8.0%) and lower percentages of CD8 + IL-4 + (0.05%) and gd + IL-4 + (0.03%) T cells.
Changes in Serum Cytokine Levels in Active Tuberculosis With Treatment
Mediators of Inflammation, 2005
It has been reported that IFN-γ, TNF-α, and IL-12 stimulate, and that IL-10, TGF-β, and IL-4 suppress the protective immune response against tuberculosis. We aim to evaluate changes in the serum levels of pro and antiinflammatory cytokines in active pulmonary tuberculosis (APTB) and the possible effects of treatment on these changes. Serum IL-12p40, IL-4, IL-10, TNF-α, IFNγ, and TGF-β1 levels were determined in 20 APTB cases (group 1) before and 2, 4, and 6 months after therapy. The same parameters were also determined in 9 inactive pulmonary tuberculosis (IPTB) cases (group 2) and 9 healthy controls (HC, group 3). Before treatment, the mean serum IFN-γ, TNF-α, and IL-10 levels in group 1 were statistically higher than those in group 2 (P = .001, P = .024, P = .016, resp) or group 3 (P = .003, P = .002, P = .011, resp). The levels in group 1 decreased significantly after treatment (P = .001 for IFN-γ, P = .004 for TNF-α, P = .000 for IL-10). The serum levels of IL-12p40 were significantly higher in group 1 than in group 3 (P = .012) and decreased insignificantly after treatment. There was no difference in serum IL-4 and TGF-β1 levels among the groups (P > .05). Because the serum IL-12p40, IL-10, TNF-α, and IFN-γ levels were high in APTB, we believe that these cytokines have important roles in the immune response to Mycobacterium tuberculosis (M tuberculosis). These parameters could be used in follow-up as indicators of the success of APTB therapy.
Clinical Infectious Diseases, 2003
We measured serum cytokine concentrations and Mycobacterium tuberculosis-stimulated cytokine production by peripheral blood mononuclear cells (PBMCs) obtained from persons infected with M. tuberculosis. Serum interferon-g (IFN-g) and interleukin-10 (IL-10) concentrations were elevated in patients with tuberculosis compared with healthy persons who had reactions to tuberculin skin tests, but IL-18 concentrations were not. In contrast, M. tuberculosis-stimulated PBMCs from patients with tuberculosis produced less IFN-g and IL-18 but similar amounts of IL-10, compared with PBMCs from healthy subjects who had reactions to tuberculin skin tests. Pretreatment of PBMCs from healthy subjects with reaction to tuberculin with serum from patients with tuberculosis inhibited IFN-g production in response to M. tuberculosis, and inhibition was blocked by anti-IL-10. Thus, serum concentrations of IFN-g, IL-18, and IL-10 do not parallel M. tuberculosis-induced cytokine levels, and increased IL-10 serum levels in patients with tuberculosis inhibit IFN-g production in response to mycobacterial antigens.