PpiA antigen specific immune response is a potential biomarker for latent tuberculosis infection

Pathakumari, Balaji; Deenadayalan, Anbarasu; Parthasarathy, Raghuveer; Raja, Alamelu

doi:10.1016/j.tube.2015.07.006

Cited by 21 publications

(20 citation statements)

References 27 publications

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“…It has been also demonstrated that there is an increased IFN‐ γ response after depletion of Treg cells in active TB . Similar to this, our previous study reported a decreased IFN‐ γ response in patients with active TB who had increased levels of Treg cells in their circulation. Further, it is evidenced that Treg cells delay the activation of CD4 + and CD8 + cells in lymph nodes, which in turn causes delayed migration of these cells to the site of infection (lungs) during TB .…”

Section: Discussionsupporting

confidence: 87%

“…The main limitation of using new antigens for immunodiagnosis is the lack of specificity for M. tuberculosis . Although, the selected antigens are also not M. tuberculosis specific, the cytokine response to these antigens was not influenced by bacillus Clamette–Guérin (BCG) vaccination as observed in our previous studies . This might be due to the fact that BCG fails to establish a long‐lived memory response against these antigens.…”

Section: Discussionmentioning

confidence: 55%

“…In our previous report, we observed that there is an impaired T‐cell response in active TB compared with LTBI . The suppressed immune response during active TB is because Treg cells play a role in immune evasion by M. tuberculosis , not because of an intrinsic defect in the T‐cell response to M. tuberculosis antigens.…”

Section: Introductionmentioning

confidence: 87%

“…The recombinant plasmids encoding ESAT‐6 and CFP‐10 were a kind gift from Colorado State University, Fort Collins, CO, USA. The proteins Rv2204c, Rv0753c and Rv0009 were cloned, over‐expressed and purified by recombinant DNA technology as described in our earlier publications . Endotoxin concentration in all recombinant protein preparations was quantified by LAL assay and ranged from 1 to 10 EU per mg of protein, which is acceptable .…”

Section: Methodsmentioning

confidence: 99%

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Altered expression of antigen‐specific memory and regulatory T‐cell subsets differentiate latent and active tuberculosis

2017

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Although one-third of the world population is infected with Mycobacterium tuberculosis, only 5-10% of the infected individuals will develop active tuberculosis (TB) disease and the rest will remain infected with no symptoms, known as latent TB infection (LTBI). Identifying biomarkers that differentiate latent and active TB disease enables effective TB control, as early detection, treatment of active TB and preventive treatment of individuals with LTBI are crucial steps involved in TB control. Here, we have evaluated the frequency of antigen-specific memory and regulatory T (Treg) cells in 15 healthy household contacts (HHC) and 15 pulmonary TB patients (PTB) to identify biomarkers for differential diagnosis of LTBI and active TB. Among all the antigens tested in the present study, early secretory antigenic target-6 (ESAT-6) -specific CD4 and CD8 central memory (Tcm) cells showed 93% positivity in HHC and 20% positivity in PTB. The novel test antigens Rv0753c and Rv0009 both displayed 80% and 20% positivity in HHC and PTB, respectively. In contrast to Tcm cells, effector memory T (Tem) cells showed a higher response in PTB than HHC; both ESAT-6 and Rv0009 showed similar positivity of 80% in PTB and 33% in HHC. PTB patients have a higher proportion of circulating antigen-reactive Treg cells (CD4 CD25 FoxP3 ) than LTBI. Rv2204c-specific Treg cells showed maximum positivity of 73% in PTB and 20% in HHC. Collectively, our data conclude that ESAT-6-specific Tcm cells and Rv2204c-specific Treg cells might be useful biomarkers to discriminate LTBI from active TB.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

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Altered expression of antigen‐specific memory and regulatory T‐cell subsets differentiate latent and active tuberculosis

2017

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“…In our observations, expansion of antigen-specific TNF-a cells was minimal in PTB with all antigen stimulations used except for CFP-10, showing the lack of these antigen-specific cells in PTB circulation. In recent times, many mycobacterial proteins have shown an equal or better Th1 response when compared with the standard antigens ESAT-6 and CFP-10 and serve as promising novel antigens for vaccine development and better diagnosis [36][37][38]. TNF-a is also important for the long-term control of TB.…”

Section: Discussionmentioning

confidence: 99%

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

Devasundaram

Raja

2017

Journal of Leukocyte Biology

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The partial effectiveness against pulmonary tuberculosis (PTB), displayed by the existing tuberculosis (TB) vaccine, bacillus Calmette-Guérin (BCG), highlights the need for novel vaccines to replace or improve BCG. In TB immunology, antigen-specific cellular immune response is frequently considered indispensable. Latency-associated antigens are intriguing as targets for TB vaccine development. The mycobacterial protein, dihydrolipoamide dehydrogenase (Lpd; Rv0462), the third enzyme of the pyruvate dehydrogenase (PDH) complex, facilitates to resist host reactive nitrogen intermediates. Multicolor flow cytometry analysis of whole-blood cultures showed higher Lpd-specific Th1 recall response (IFN-γ, TNF-α, and IL-2; = 0.0006) and memory CD4 and CD8 T cells (CCR7 CD45RA and CCR7 CD45RA) in healthy household contacts (HHC) of TB ( < 0.0001), which is comparable with or higher than the standard antigens, ESAT-6 and CFP-10. The frequency of Lpd-specific multifunctional T cells was higher in HHC compared with PTB patients. However, there is no significant statistical correlation. Regulatory T cell (T) analysis of HHCs and active TB patients demonstrated very low Lpd-specific CD4 T relative to ESAT-6 and CFP-10. Our study demonstrates that the Lpd antigen induces a strong cellular immune response in healthy mycobacteria-infected individuals. In consideration of this population having demonstrated immunologic protection against active TB disease development, our data are encouraging about the possible use of Lpd as a target for further TB subunit vaccine development.

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Host‐pathogen dialogues in different cell death modes during Mycobacterium tuberculosis infection

Ruan,

Lyu,

Lai

et al. 2024

Interdisciplinary Medicine

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Tuberculosis (TB) is a fatal infectious disease that continues to pose a serious public health threat. The emergence of drug‐resistant TB has further worsened the burden of the disease. The interaction between the host and the pathogen involves multiple modes of cell death, which play a role in determining immune outcomes. Several studies have established a strong correlation between cell death and TB progression. This review explores the molecular mechanisms of various cell death modes in Mycobacterium tuberculosis (Mtb) infection and how Mtb's virulence effectors regulate these pathways, including apoptosis, autophagy, pyroptosis, ferroptosis, and necrosis. Furthermore, therapeutic strategies targeting cell death pathways have shown promising results in TB treatment. Importantly, this review highlights the significant potential of mitochondria in mediating communication between different cell death modes and influencing the final outcomes. Overall, this work provides a comprehensive summary of the role of cell death in host immune responses and immune evasion by Mtb. It also offers valuable insights into the pathogenesis of TB and immune evasion strategies employed by Mtb and contributes to the development of more effective anti‐TB therapies.

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PpiA antigen specific immune response is a potential biomarker for latent tuberculosis infection

Cited by 21 publications

References 27 publications

Altered expression of antigen‐specific memory and regulatory T‐cell subsets differentiate latent and active tuberculosis

Altered expression of antigen‐specific memory and regulatory T‐cell subsets differentiate latent and active tuberculosis

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

Host‐pathogen dialogues in different cell death modes during Mycobacterium tuberculosis infection

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