Interleukin-7 Unveils Pathogen-Specific T Cells by Enhancing Antigen-Recall Responses

Terrazzini, Nadia; Mantegani, Paola; Kern, Florian; Fortis, Claudio; Mondino, Anna; Caserta, Stefano

doi:10.1093/infdis/jiy096

Cited by 8 publications

(9 citation statements)

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“…Polymorphisms of the IL-1ra gene on chromosome 2 have been shown to be associated with genetic susceptibility to TB amongst Gambians and a higher IL-1ra/IL-1β ratio in response to M.tb indicates the inflammatory profile of an individual [ 43 , 44 ]. IL-7 is a pleiotropic growth factor that binds to the IL-7 receptor (IL-7R) and promotes the generation, expansion and survival of T-cells, and decreases the production of TGF-β [ 45 , 46 ]. Its production was shown to increase in the lung tissues of non-human primates that also showed increased survival following M.tb challenge [47] .…”

Section: Discussionmentioning

confidence: 99%

A three-marker protein biosignature distinguishes tuberculosis from other respiratory diseases in Gambian children

et al. 2020

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Background Our study aimed to identify a host cytokine biosignature that could distinguish childhood tuberculosis (TB) from other respiratory diseases (OD). Methods Cytokine responses in prospectively recruited children with symptoms suggestive of TB were measured in whole blood assay supernatants, harvested after overnight incubation, using a Luminex platform. We used logistic regression models with Least Absolute Shrinkage and Selection Operator (LASSO) penalty to identify the optimal biosignature associated with confirmed TB disease in the training set. We subsequently assessed its performance in the test set. Findings Of the 431 children included in the study, 44 had bacteriologically confirmed TB, 60 had clinically diagnosed TB while 327 had OD. All children were HIV-negative. Application of LASSO regression models to the training set ( n = 260) resulted in the combination of IL-1ra, IL-7 and IP-10 from unstimulated samples as the optimally discriminant cytokine biosignature associated with bacteriologically confirmed TB. In the test set ( n = 171), this biosignature distinguished children diagnosed with TB disease, irrespective of microbiological confirmation, from OD with area under the receiver operator characteristic curve (AUC) of 0•74 (95% CI: 0•67, 0•81), and demonstrated sensitivity and specificity of 72•2% (95% CI: 60•4, 82•1%) and 75•0% (95% CI: 64•9, 83•4%) respectively, with its performance independent of their age group and their age- and sex-adjusted nutritional status. Interpretation This novel biosignature of childhood TB derived from unstimulated supernatants is promising. Independent validation with further optimisation will improve its performance and translational potential. Funding Steinberg Fellowship (McGill University); Grand Challenges Canada; MRC Program Grant.

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Section: Discussionmentioning

confidence: 99%

A three-marker protein biosignature distinguishes tuberculosis from other respiratory diseases in Gambian children

et al. 2020

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“…25 In addition, a recent study showed IL-7 activity in enhancing cytokine-producing CD4 pathogenspecific T cells, such as M. tuberculosis. 26 Thus, we hypothesize that M. leprae antigenic stimulation might increase IL-7 in ENL patients and could be able to induce a synergic effect in cytokine-producing memory T cells.…”

Section: Discussionmentioning

confidence: 93%

Involvement of TNF-Producing CD8+ Effector Memory T Cells with Immunopathogenesis of Erythema Nodosum Leprosum in Leprosy Patients

Silva

Santos

Mendes

et al. 2019

The American Journal of Tropical Medicine and Hygiene

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Type 2 reaction (T2R) or erythema nodosum leprosum (ENL), a sudden episode of acute inflammation predominantly affecting lepromatous leprosy patients (LL), characterized by a reduced cellular immune response. This possibly indicates a close relationship between the onset of T2R and the altered frequency, and functional activity of T lymphocytes, particularly of memory subsets. This study performed ex vivo and in vitro characterizations of T cell blood subpopulations from LL patients with or without T2R. In addition, the evaluation of activity of these subpopulations was performed by analyzing the frequency of these cells producing IFN-γ, TNF, and IL-10 by flow cytometry. Furthermore, the expression of transcription factors, for the differentiation of T cells, were analyzed by quantitative real-time polymerase chain reaction. Our results showed an increased frequency of CD8 + /TNF + effector memory T cells (T EM ) among T2Rs. Moreover, there was evidence of a reduced frequency of CD4 and CD8 + IFN-γ-producing cells in T2R, and a reduced expression of STAT4 and TBX21. Finally, a significant and positive correlation between bacteriological index (BI) of T2R patients and CD4 + /TNF + and CD4 + /IFN-γ + T cells was observed. Thus, negative correlation between BI and the frequency of CD4 + /IL-10 + T cells was noted. These results suggest that CD8 + /TNF + T EM are primarily responsible for the transient alteration in the immune response to Mycobacterium leprae in ENL patients. Thus, our study improves our understanding of pathogenic mechanisms and might suggest new therapeutic approaches for leprosy.Note: Supplemental table and figure appear at www.ajtmh.org.

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“…IP-10 and BCA-1 are two chemokines with chemoattractant properties over cells expressing the receptor CXCR3 [34,35], which include Th1 cells, one of the major participants in cellular immunity against M. tuberculosis infection [36]. IL-7, on the other hand, has been associated with enhanced recall responses of Mtb-specific CD4 + T cells in vitro [37], therefore suggesting a protective role. However, other studies described an impaired T-cell sensitivity to IL-7, with decreased soluble and membrane-bound IL-7 receptor and increased IL-7 plasma concentrations in TB [38].…”

Section: Discussionmentioning

confidence: 99%

“…tuberculosis infection [ 36 ]. IL-7, on the other hand, has been associated with enhanced recall responses of Mtb -specific CD4 + T cells in vitro [ 37 ], therefore suggesting a protective role. However, other studies described an impaired T-cell sensitivity to IL-7, with decreased soluble and membrane-bound IL-7 receptor and increased IL-7 plasma concentrations in TB [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of candidate host serum and saliva biomarkers for a better diagnosis of active and latent tuberculosis infection

et al. 2020

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In our work, we aim to identify new candidate host biomarkers to discriminate between active TB patients (n = 28), latent infection (LTBI; n = 27) and uninfected (NoTBI; n = 42) individuals. For that, active TB patients and their contacts were recruited that donated serum and saliva samples. A multiplex assay was performed to study the concentration of different cytokines, chemokines and growth factors. Proteins with significant differences between groups were selected and logistic regression and the area under the ROC curve (AUC) was used to assess the diagnostic accuracy. The best marker combinations that discriminate active TB from NoTBI contacts were [IP-10 + IL-7] in serum and [Fractalkine + IP-10 + IL-1α + VEGF] in saliva. Best discrimination between active TB and LTBI was achieved using [IP-10 + BCA-1] in serum (AUC = 0.83) and IP-10 in saliva (p = 0.0007; AUC = 0.78). The levels of TNFα (p = 0.003; AUC = 0.73) in serum and the combination of [Fractalkine +IL-12p40] (AUC = 0.83) in saliva, were able to differentiate between NoTBI and LTBI contacts. In conclusion, different individual and combined protein markers could help to discriminate between active TB and both uninfected and latently-infected contacts. The most promising ones include [IP-10 + IL-7], [IP-10 + BCA-1] and TNFα in serum and [Fractalkine + IP-10 + IL-1α + VEGF], IP-10 and [Fractalkine+IL-12p40] in saliva.

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Interleukin-7 Unveils Pathogen-Specific T Cells by Enhancing Antigen-Recall Responses

Cited by 8 publications

References 50 publications

A three-marker protein biosignature distinguishes tuberculosis from other respiratory diseases in Gambian children

A three-marker protein biosignature distinguishes tuberculosis from other respiratory diseases in Gambian children

Involvement of TNF-Producing CD8+ Effector Memory T Cells with Immunopathogenesis of Erythema Nodosum Leprosum in Leprosy Patients

Identification of candidate host serum and saliva biomarkers for a better diagnosis of active and latent tuberculosis infection

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