Changes in Host Cytokine Patterns of TB Patients with Different Bacterial Loads Detected Using 16S rRNA Analysis

Heslop, Rhiannon; Bojang, Adama; Jarju, Sheikh; Mendy, Joseph; Mulwa, Sarah; Secka, Ousman; Mendy, Francis; Owolabi, Olumuyiwa; Kampmann, Beate; Sutherland, Jayne S.

doi:10.1371/journal.pone.0168272

Cited by 12 publications

(7 citation statements)

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“…We used 16 S rRNA mycobacterial load assay to determine viable bacilli counts in sputum samples of TB/Flu co-infected subjects as recently published by our laboratory (15) We saw a significant increase in bacterial load in TB/Flu co-infected patients compared to those with TB mono-infection (median [Interquartile range (IQR)] 2.5E5 [0.9E5-16E5] cfu/ml for co-infected compared to 0.5E5 [0.1E5-2E5]; p = 0.0026; Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Changes in Mycobacterium tuberculosis-Specific Immunity With Influenza co-infection at Time of TB Diagnosis

et al. 2019

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Background: Prior Influenza A viral (IAV) infection has been shown to increase susceptibility to tuberculosis (TB) and TB has also been shown to be a primary cause of death during pandemics, including the Spanish Influenza outbreak of 1918–1919. The majority of data has been obtained from mouse models, thus the aim of this study was to determine the impact of Flu co-infection on host immunity and disease severity in TB patients at diagnosis.Methods: Sputum from 282 patients with active TB were analyzed for presence of FluA/FluB RNA at presentation using multiplex PCR. Sputum RNA was also analyzed for Mycobacterium tuberculosis (Mtb) load using 16S RNA amplification. Supernatants from digested sputum and Mtb antigen-stimulated whole blood were analyzed using multiplex cytokine arrays and PBMC were analyzed for cytokine production from CD4+ T, CD8+ T and Mucosal Associated Invariant T cells (MAITs).Results: 12 (4.3%) of TB patients were found to have FluA or FluB viral RNA present in their sputum at the time of TB diagnosis. The TB/Flu co-infected patients had a significantly higher bacterial load compared to those with TB mono-infection (p = 0.0026). They had lower levels of IL17A in ex vivo sputum (p = 0.0275) and higher MCP-1 (CCL2) levels in the blood following PPD stimulation (p = 0.0267). TB/Flu co-infected subjects had significantly higher IFN-γ+IL-17+CD4+ and IFN-γ+IL-17-CD8+ cells compared to TB mono-infected subjects.Conclusions: These data show that Flu co-infection at time of TB diagnosis is associated with a higher bacterial load and differential cellular and soluble profiles. These findings show for the first time the impact of TB/Flu co-infection in a human cohort and support the potential benefit of Flu vaccination in TB-endemic settings.

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Section: Resultsmentioning

confidence: 99%

Changes in Mycobacterium tuberculosis-Specific Immunity With Influenza co-infection at Time of TB Diagnosis

et al. 2019

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“…We additionally examined the cytokine/chemokine levels known to be associated with inflammation and cell repair [25][26][27][28]. In each of two experiments, we found that the cytokines/chemokines were altered both by the diets and by the CFA/DNA/PEP insults (results of one representative experiment are shown in Figure 2).…”

Section: Abnormal Immunoglobulin and Cytokine/chemokine Profiles In Vmentioning

confidence: 99%

Consequences of Vitamin A Deficiency: Immunoglobulin Dysregulation, Squamous Cell Metaplasia, Infectious Disease, and Death

Surman

Penkert

Sealy

et al. 2020

IJMS

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Vitamin A is an important regulator of immune protection, but it is often overlooked in studies of infectious disease. Vitamin A binds an array of nuclear receptors (e.g., retinoic acid receptor, peroxisome proliferator-activated receptor, retinoid X receptor) and influences the barrier and immune cells responsible for pathogen control. Children and adults in developed and developing countries are often vitamin A-deficient or insufficient, characteristics associated with poor health outcomes. To gain a better understanding of the protective mechanisms influenced by vitamin A, we examined immune factors and epithelial barriers in vitamin A deficient (VAD) mice, vitamin D deficient (VDD) mice, double deficient (VAD+VDD) mice, and mice on a vitamin-replete diet (controls). Some mice received insults, including intraperitoneal injections with complete and incomplete Freund’s adjuvant (emulsified with PBS alone or with DNA + Fus-1 peptide) or intranasal inoculations with Sendai virus (SeV). Both before and after insults, the VAD and VAD+VDD mice exhibited abnormal serum immunoglobulin isotypes (e.g., elevated IgG2b levels, particularly in males) and cytokine/chemokine patterns (e.g., elevated eotaxin). Even without insult, when the VAD and VAD+VDD mice reached 3–6 months of age, they frequently exhibited opportunistic ascending bacterial urinary tract infections. There were high frequencies of nephropathy (squamous cell hyperplasia of the renal urothelium, renal scarring, and ascending pyelonephritis) and death in the VAD and VAD+VDD mice. When younger VAD mice were infected with SeV, the predominant lesion was squamous cell metaplasia of respiratory epithelium in lungs and bronchioles. Results highlight a critical role for vitamin A in the maintenance of healthy immune responses, epithelial cell integrity, and pathogen control.

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“…Several of the studies were longitudinal, making it evident that the immune substances changed during the administration of TB treatment [82,83]. Changes in lung bacterial load related to treatment administration would appear to influence the concentration of cytokines detected in nonstimulated cells, with 17 out of the 27 cytokines/chemokines analyzed (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-13, IL-17, eotaxin, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF, RANTES, and VEGF) being significantly lower in patients with higher bacterial load and levels of IL10, IL15, and TNF-α being higher in the same patients [84].…”

Section: Discussionmentioning

confidence: 92%

Gaps in Study Design for Immune Parameter Research for Latent Tuberculosis Infection: A Systematic Review

Herrera

Vera

Keynan

et al. 2020

Journal of Immunology Research

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Background. Immune parameters (IP) have been extensively studied to distinguish between latent tuberculosis (LTBI) and active tuberculosis (TB). Objective. To determine the IP associated with LTBI, compared to active TB and individuals not infected by M. tuberculosis published in literature. Methods. We conducted a systematic search using Google Scholar and PubMed databases, combining the MeSH terms latent tuberculosis, Mycobacterium tuberculosis, cytokines, and biological markers, with the free terms, biomarkers and cytokines. Spanish, English, and Portuguese articles comparing the concentration of IP associated with LTBI, either in plasma/serum or in vitro, in adults and nonimmunocompromised versus individuals with TB or without M. tuberculosis infection between 2006 July and 2018 July were included. Two blinded reviewers carried out the searches, read the abstracts, and selected the articles for analysis. Participants’ information, diagnostic criteria, IP, detection methods, and biases were collected. Results. We analyzed 36 articles (of 637 abstracts) with 93 different biomarkers in different samples. We found 24 parameters that were increased only in active TB (TGF-α, CSF3, CSF2, CCL1 [I-309], IL-7, TGF-β1, CCL3 [MIP-1α], sIL-2R, TNF-β, CCL7 [MCP-3], IFN-α, fractalkine, I-TAG, CCL8 [MCP-2], CCL21 [6Ckine], PDGF, IL-22, VEGF-A, LXA4, PGE2, PGF2α, sCD163, sCD14, and 15-Epi-LXA4), five were elevated in LTBI (IL-5, IL-17F, IL-1, CCL20 [MIP-3α], and ICAM-1), and two substances were increased among uninfected individuals (IL-23 and basic FGF). We found high heterogeneity between studies including failure to account for the time/illness of the individuals studied; varied samples and protocols; different clinical classification of TB; different laboratory methods for IP detection, which in turn leads to variable units of measurement and assay sensitivities; and selection bias regarding TST and booster effect. None of the studies adjusted the analysis for the effect of ethnicity. Conclusions. It is mandatory to harmonize the study of immune parameters for LTBI diagnosis. This systematic review is registered with PROSPERO CRD42017073289.

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Changes in Host Cytokine Patterns of TB Patients with Different Bacterial Loads Detected Using 16S rRNA Analysis

Cited by 12 publications

References 12 publications

Changes in Mycobacterium tuberculosis-Specific Immunity With Influenza co-infection at Time of TB Diagnosis

Changes in Mycobacterium tuberculosis-Specific Immunity With Influenza co-infection at Time of TB Diagnosis

Consequences of Vitamin A Deficiency: Immunoglobulin Dysregulation, Squamous Cell Metaplasia, Infectious Disease, and Death

Gaps in Study Design for Immune Parameter Research for Latent Tuberculosis Infection: A Systematic Review

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