Dihydrolipoamide dehydrogenase-Lpd (Rv0462)-specific T cell recall responses are higher in healthy household contacts of TB: a novel immunodominant antigen from <i>M. tuberculosis</i>

Devasundaram, Santhi; Raja, Alamelu

doi:10.1189/jlb.4a0916-067rr

Cited by 7 publications

(3 citation statements)

References 57 publications

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“…tuberculosis had significantly increased M . tuberculosis IFN-γ and IL-2 responses compared to non-infected individuals, which is expected, as IFN-γ and IL-2 profiles have been associated with antigenic memory 22–24 . Furthermore, the IL-8 response was significantly higher in HCWs LTB+ compared to HCWs LTB− and CCs LTB− .…”

Section: Discussionmentioning

confidence: 56%

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

Essone¹,

Leboueny²,

Siawaya³

et al. 2019

Sci Rep

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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 anti-inflammatory/T...

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Section: Discussionmentioning

confidence: 56%

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

Essone¹,

Leboueny²,

Siawaya³

et al. 2019

Sci Rep

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“…Characteristics such as slower growth and increased membrane fluidity also occur in PDC-deficient Staphylococcus aureus, indicating a structural impact of the enzyme 68 . PDC-E2 has been also proposed as a target for antibiotic treatment 69,70 and vaccine development 71 for M. tuberculosis. However, up to date, no study has evaluated the impact of PDC from Listeria spp.…”

Section: Discussionmentioning

confidence: 99%

Pyruvate dehydrogenase complex—enzyme 2, a new target for Listeria spp. detection identified using combined phage display technologies

Moreira

Köllner

Helmsing

et al. 2020

Sci Rep

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The genus Listeria comprises ubiquitous bacteria, commonly present in foods and food production facilities. In this study, three different phage display technologies were employed to discover targets, and to generate and characterize novel antibodies against Listeria: antibody display for biomarker discovery and antibody generation; ORFeome display for target identification; and single-gene display for epitope characterization. With this approach, pyruvate dehydrogenase complex—enzyme 2 (PDC-E2) was defined as a new detection target for Listeria, as confirmed by immunomagnetic separation-mass spectrometry (IMS-MS). Immunoblot and fluorescence microscopy showed that this protein is accessible on the bacterial cell surface of living cells. Recombinant PDC-E2 was produced in E. coli and used to generate 16 additional antibodies. The resulting set of 20 monoclonal scFv-Fc was tested in indirect ELISA against 17 Listeria and 16 non-Listeria species. Two of them provided 100% sensitivity (CI 82.35–100.0%) and specificity (CI 78.20–100.0%), confirming PDC-E2 as a suitable target for the detection of Listeria. The binding region of 18 of these antibodies was analyzed, revealing that ≈ 90% (16/18) bind to the lipoyl domains (LD) of the target. The novel target PDC-E2 and highly specific antibodies against it offer new opportunities to improve the detection of Listeria.

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“…GAPDH is also an adhesion-associated factor and exists in most invasive isolates, including serotypes 1, 2, 7, and 9 [15]. Moreover, the surface-exposed immune evasion protein DLD is a potential vaccine antigen against Vibrio and M. tuberculosis [16,17]. To date, no research has focused on the protective immunity of DLD in S. suis.…”

Section: Introductionmentioning

confidence: 99%

TLR4 Agonist Combined with Trivalent Protein JointS of Streptococcus suis Provides Immunological Protection in Animals

et al. 2021

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Streptococcus suis (S. suis) serotype 2 (SS2) is the causative agent of swine streptococcosis and can cause severe diseases in both pigs and humans. Although the traditional inactive vaccine can protect pigs from SS2 infection, novel vaccine candidates are needed to overcome its shortcomings. Three infection-associated proteins in S. suis—muramidase-released protein (MRP), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and DLD, a novel putative dihydrolipoamide dehydrogenase—have been previously identified by immunoproteomic assays. In this study, the effective immune protection of the recombinant trivalent protein GAPDH-MRP-DLD (JointS) against SS2, SS7, and SS9 was determined in zebrafish. To improve the immune efficacy of JointS, monophosphoryl lipid A (MPLA) as a TLR4 agonist adjuvant, which induces a strong innate immune response in the immune cells of mice and pigs, was combined with JointS to immunize the mice. The results showed that immunized mice could induce the production of a high titer of anti-S. suis antibodies; as a result, 100% of mice survived after SS2 infection. Furthermore, JointS provides good protection against virulent SS2 strain infections in piglets. Given the above, there is potential to develop JointS as a novel subunit vaccine for piglets to prevent infection by SS2 and other S. suis serotypes.

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Dihydrolipoamide dehydrogenase-Lpd (Rv0462)-specific T cell recall responses are higher in healthy household contacts of TB: a novel immunodominant antigen from M. tuberculosis

Cited by 7 publications

References 57 publications

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

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

Pyruvate dehydrogenase complex—enzyme 2, a new target for Listeria spp. detection identified using combined phage display technologies

TLR4 Agonist Combined with Trivalent Protein JointS of Streptococcus suis Provides Immunological Protection in Animals

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