Successful TB treatment induces B-cells expressing FASL and IL5RA mRNA

Rensburg, Ilana C. van; Wagman, Chandre; Stanley, Kim; Beltran, Caroline G. G.; Ronacher, Katharina; Walzl, Gerhard; Loxton, André G.

doi:10.18632/oncotarget.12184

Cited by 23 publications

(22 citation statements)

References 23 publications

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“…The results indicated that there is an increase in the levels of both genes by month 6 of treatment. In a previous study, we found that the levels of FasL and Il5Ra of the untreated TB cases were lower when we compared it to that of community controls (data not shown) . These results correlate with the phenotypic results which indicates that there is an increase in the surface expression of FASL and IL5RA during treatment, even though those changes are not statistically significant.…”

Section: Discussionsupporting

confidence: 59%

B‐cells with a FasL expressing regulatory phenotype are induced following successful anti‐tuberculosis treatment

Rensburg

Kleynhans

Keyser

et al. 2016

Immunity Inflam & Disease

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IntroductionStudies show that B‐cells, in addition to producing antibodies and antigen‐presentation, are able to produce cytokines as well. These include regulatory cytokines such as IL‐10 by regulatory B‐cells. Furthermore, a rare regulatory subset of B‐cells have the potential to express FasL, which is a death‐inducing ligand. This subset of B‐cells have a positive role during autoimmune disease, but has not yet been studied during tuberculosis. These FasL‐expressing B‐cells are induced by bacterial LPS and CpG, thus we hypothesized that this phenotype might be induced during tuberculosis as well.MethodsB‐cells from participants with TB (at diagnosis and during treatment) and controls were collected, and analyzed by means of real‐time PCR and flow cytometry. In addition to this, BAL was collected from TB participants as well and analyzed by means of MAGPix (multi‐cytokine) technology.ResultsGene expression analysis show that FASL transcript levels increase by the end of treatment. Similarly, phenotypic analysis show that there is a higher frequency of FasL‐expressing B‐cells by the end of treatment.ConclusionCollectively, these results indicate that these FasL‐expressing B‐cells are being induced during anti‐TB treatment, and thus may play a positive role. Further studies are required to elucidate this.

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Section: Discussionsupporting

confidence: 59%

B‐cells with a FasL expressing regulatory phenotype are induced following successful anti‐tuberculosis treatment

Rensburg

Kleynhans

Keyser

et al. 2016

Immunity Inflam & Disease

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“…Recently IL5RA was found to be under-expressed in human tuberculosis (TB) patients compared with healthy controls [33]. Further, after 2 and 6 months of treatment for TB, IL5RA was found overexpressed in the treated patient group compared to the healthy controls, indicating a reactivation of the immune cells [33]. This is in line with the present study, where this gene is significantly under-expressed in the para-tuberculosis infected and exposed samples compared with controls.…”

Section: Discussionsupporting

confidence: 90%

“…IL5 is a cytokine that acts as a growth and differentiation factor for both B cells and eosinophils. Recently IL5RA was found to be under-expressed in human tuberculosis (TB) patients compared with healthy controls [33]. Further, after 2 and 6 months of treatment for TB, IL5RA was found overexpressed in the treated patient group compared to the healthy controls, indicating a reactivation of the immune cells [33].…”

Section: Discussionmentioning

confidence: 99%

Combinatorial Discriminant Analysis Applied to RNAseq Data Reveals a Set of 10 Transcripts as Signatures of Exposure of Cattle to Mycobacterium avium subsp. paratuberculosis

Malvisi

Curti²,

Remondini³

et al. 2020

Animals

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Paratuberculosis or Johne’s disease in cattle is a chronic granulomatous gastroenteritis caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP). Paratuberculosis is not treatable; therefore, the early identification and isolation of infected animals is a key point to reduce its incidence. In this paper, we analyse RNAseq experimental data of 5 ELISA-negative cattle exposed to MAP in a positive herd, compared to 5 negative-unexposed controls. The purpose was to find a small set of differentially expressed genes able to discriminate between exposed animals in a preclinical phase from non-exposed controls. Our results identified 10 transcripts that differentiate between ELISA-negative, clinically healthy, and exposed animals belonging to paratuberculosis-positive herds and negative-unexposed animals. Of the 10 transcripts, five (TRPV4, RIC8B, IL5RA, ERF, CDC40) showed significant differential expression between the three groups while the remaining 5 (RDM1, EPHX1, STAU1, TLE1, ASB8) did not show a significant difference in at least one of the pairwise comparisons. When tested in a larger cohort, these findings may contribute to the development of a new diagnostic test for paratuberculosis based on a gene expression signature. Such a diagnostic tool could allow early interventions to reduce the risk of the infection spreading.

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“…Those authors also reported increased BAFF expression levels in pleural effusions of M. tuberculosis-infected patients with pleurisy. In another study, APRIL expression was shown to be increased in B cells of M. tuberculosis-infected patients after 6 months of anti-M. tuberculosis treatment (140). Finally, a recent study confirmed the BAFF-and APRIL-inducing effect of M. tuberculosis by measuring serum BAFF and APRIL levels in patients with latent M. tuberculosis infection (141).…”

Section: Bacteria Bacterial Infections Of the Respiratory Systemmentioning

confidence: 89%

The Role of BAFF System Molecules in Host Response to Pathogens

Sakai

Akkoyunlu

2017

Clin Microbiol Rev

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The two ligands B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) and the three receptors BAFF receptor (BAFF-R), transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI), and B cell maturation antigen (BCMA) are members of the "BAFF system molecules." BAFF system molecules are primarily involved in B cell homeostasis. The relevance of BAFF system molecules in host responses to microbial assaults has been investigated in clinical studies and in mice deficient for each of these molecules. Many microbial products modulate the expression of these molecules. Data from clinical studies suggest a correlation between increased expression levels of BAFF system molecules and elevated B cell responses. Depending on the pathogen, heightened B cell responses may strengthen the host response or promote susceptibility. Whereas pathogen-mediated increases in the expression levels of the ligands and/or the receptors appear to promote microbial clearance, certain pathogens have evolved to ablate B cell responses by suppressing the expression of TACI and/or BAFF-R on B cells. Other than its well-established role in B cell responses, the TACI-mediated activation of macrophages is also implicated in resistance to intracellular pathogens. An improved understanding of the role that BAFF system molecules play in infection may assist in devising novel strategies for vaccine development.

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Successful TB treatment induces B-cells expressing FASL and IL5RA mRNA

Cited by 23 publications

References 23 publications

B‐cells with a FasL expressing regulatory phenotype are induced following successful anti‐tuberculosis treatment

B‐cells with a FasL expressing regulatory phenotype are induced following successful anti‐tuberculosis treatment

Combinatorial Discriminant Analysis Applied to RNAseq Data Reveals a Set of 10 Transcripts as Signatures of Exposure of Cattle to Mycobacterium avium subsp. paratuberculosis

The Role of BAFF System Molecules in Host Response to Pathogens

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