Type 2 Diabetes Mellitus and Latent Tuberculosis Infection Moderately Influence Innate Lymphoid Cell Immune Responses in Uganda

Ssekamatte, Phillip; Nakibuule, Marjorie; Nabatanzi, Rose; Egesa, Moses; Musubika, Carol; Bbuye, Mudarshiru; Hepworth, Matthew R.; Doherty, Derek G.; Cose, Stephen; Andia-Biraro, Irene

doi:10.3389/fimmu.2021.716819

Cited by 11 publications

(10 citation statements)

References 79 publications

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“…In accordance with the findings in previous studies [9,36], this study revealed significantly lower plasma levels of TNF-α and IL-17 in DM patients with LTBI than non-LTBI counterparts, suggesting increased TB susceptibility through the decreasing phagocytic ability of macrophages, interference with granuloma formation [37] and inhibiting Mtb-specific memory responses [38]. We though herein demonstrated the significant correlation between Th1-and Th17-related cytokines and the 6 most differentially abundant taxa of gut microbiota, further studies should be conducted to explore the immunomodulatory effect of gut microbiome on Mtb infection.…”

Section: Discussionsupporting

confidence: 93%

Gut microbiota composition can reflect immune responses of latent tuberculosis infection in patients with poorly controlled diabetes

Huang

Luo

et al. 2023

Respir Res

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Background Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB). Evidence has linked the DM-related dysbiosis of gut microbiota to modifiable host immunity to Mycobacterium tuberculosis infection. However, the crosslinks between gut microbiota composition and immunological effects on the development of latent TB infection (LTBI) in DM patients remain uncertain. Methods We prospectively obtained stool, blood samples, and medical records from 130 patients with poorly-controlled DM (pDM), defined as ever having an HbA1c > 9.0% within previous 1 year. Among them, 43 had LTBI, as determined by QuantiFERON-TB Gold in-Tube assay. The differences in the taxonomic diversity of gut microbiota between LTBI and non-LTBI groups were investigated using 16S ribosomal RNA sequencing, and a predictive algorithm was established using a random forest model. Serum cytokine levels were measured to determine their correlations with gut microbiota. Results Compared with non-LTBI group, the microbiota in LTBI group displayed a similar alpha-diversity but different beta-diversity, featuring decrease of Prevotella_9, Streptococcus, and Actinomyces and increase of Bacteroides, Alistipes, and Blautia at the genus level. The accuracy was 0.872 for the LTBI prediction model using the aforementioned 6 microbiome-based biomarkers. Compared with the non-LTBI group, the LTBI group had a significantly lower serum levels of IL-17F (p = 0.025) and TNF-α (p = 0.038), which were correlated with the abundance of the aforementioned 6 taxa. Conclusions The study results suggest that gut microbiome composition maybe associated with host immunity relevant to TB status, and gut microbial signature might be helpful for the diagnosis of LTBI.

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Section: Discussionsupporting

confidence: 93%

Gut microbiota composition can reflect immune responses of latent tuberculosis infection in patients with poorly controlled diabetes

Huang

Luo

et al. 2023

Respir Res

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“…26 Conversely, type 2 diabetes patients infected with tuberculosis exhibited an obvious reduction in circulating ILC3s relative to those without diabetes. 27 Additionally, ILC3s have been shown to participate in the progression of other metabolic diseases, such as fatty liver disease. 28 Despite the increased levels of circulating ILC3s in HUA patients observed in this study, whether or not ILC3s contribute to HUA development requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Type 3 innate lymphoid cells as an indicator of renal dysfunction and serum uric acid in hyperuricemia

Chen¹,

Liu²,

Wang³

et al. 2022

Adv Clin Exp Med

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Background. Type 3 innate lymphoid cells (ILC3s) are a newly identified group of innate immune cells that participate in the progression of several metabolic diseases by secreting interleukin (IL)-17 and IL-22. These cytokines are associated with hyperuricemia (HUA) severity and development; however, the relationship between ILC3s and HUA remains unclear.Objectives. To determine the characteristics of circulating ILC3s in patients with HUA.Materials and methods. Type 3 innate lymphoid cells and their subsets were detected using flow cytometry in peripheral blood mononuclear cells (PBMCs) of 80 HUA patients and 30 healthy controls (HC). Plasma levels of IL-17A and IL-22 were measured with enzyme-linked immunosorbent assay (ELISA). Clinical data of enrolled subjects were collected from electronic medical records. Results.In patients with HUA, the frequency of circulating ILC3s was elevated and positively correlated with levels of serum uric acid and serum creatinine (Scr). Although there was no significant difference in the plasma concentration of IL-17A between the patients with HUA and healthy controls, positive correlations between plasma IL-17A and the concentration of serum uric acid and frequency of circulating ILC3s were observed in the patients with HUA. Conclusions.In patients with HUA, positive correlations were detected between circulating ILC3 levels, plasma IL-17A and serum uric acid. Therefore, ILC3s and IL-17A may be useful indicators of disease severity, and are potential new therapeutic targets in HUA.

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“…It indicated participants with C-TST conversion in the baseline IGRA-negative group are more inclined to the true LTBI status. T2DM patients may have a false-negative TST or C-TST due to immunosuppression ( 12 , 33 ). However, the use of the booster effect to increase the detection of LTBI had been recommended in different populations, including immunosuppressed patients as well as healthy population ( 34 – 36 ).…”

Section: Discussionmentioning

confidence: 99%

Serial testing of latent tuberculosis infection in patients with diabetes mellitus using interferon-gamma release assay, tuberculin skin test, and creation tuberculin skin test

Cao

Guo

et al. 2022

Front. Public Health

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BackgroundDiabetes mellitus (DM) patients with latent tuberculosis infection (LTBI) have an increased risk of developing active tuberculosis (TB) due to impaired immunity. The performance of currently available immune response-based assays for identification of TB infection had been rarely evaluated in patients with type 2 DM (T2DM) in China.MethodsA prospective study was conducted to investigate the status of LTBI in patients with confirmed T2DM. At the baseline survey, the prevalence of LTBI was tested using interferon-gamma release assay (IGRA), tuberculin skin test (TST) and creation tuberculin skin test (C-TST) in parallel. After a 3-month interval, the participants were retested by the three assays to estimate their performance in the serial testing.ResultsA total of 404 participants with T2DM were included in the study. At baseline, after excluding active TB, the prevalence of LTBI identified by TST (≥ 10 mm), C-TST (≥ 5 mm) and IGRA (≥ 0.35 IU/ml) were 9.65% (39/404), 10.40% (42/404) and 14.85% (60/404), respectively. The concordance of TST and C-TST results with IGRA results was 86.39% (349/404) and 92.08% (372/404) with a Kappa coefficient of 0.37 [95% confidence interval (CI): 0.24– 0.50] and 0.64 (95% CI: 0.53– 0.76), respectively. After a 3-month interval, the continuous results of TST, C-TST and IGRA were observed to be increased with testing conversion for 50, 26 and 27 patients, respectively. For TST and C-TST conversions, the distribution of their quantitative results in serial tests varied significantly when further classified by baseline IGRA dichotomous results.ConclusionIn studied patients with T2DM, C-TST showed higher consistency with IGRA as compared to TST. The present of conversion observed in serial testing suggested that boosting effect of skin testing should be considered for identify of LTBI in patients with T2DM.

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Type 2 Diabetes Mellitus and Latent Tuberculosis Infection Moderately Influence Innate Lymphoid Cell Immune Responses in Uganda

Cited by 11 publications

References 79 publications

Gut microbiota composition can reflect immune responses of latent tuberculosis infection in patients with poorly controlled diabetes

Gut microbiota composition can reflect immune responses of latent tuberculosis infection in patients with poorly controlled diabetes

Type 3 innate lymphoid cells as an indicator of renal dysfunction and serum uric acid in hyperuricemia

Serial testing of latent tuberculosis infection in patients with diabetes mellitus using interferon-gamma release assay, tuberculin skin test, and creation tuberculin skin test

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