Transforming Growth Factor-β Decreases Survival of Mycobacterium bovis-Activated T Cells

Hernández-Garay, Marisol; Méndez-Samperio, Patricia

doi:10.1016/s0188-4409(02)00463-0

Cited by 9 publications

(5 citation statements)

References 31 publications

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“…The TGF-β signaling pathway is known to limit CD4 + T lymphocyte proliferation by reducing the effects of CD28 co-stimulation 55 and TGF-β has previously been shown to regulate the lymphocyte response to mycobacterial infection in mice 56 . TGF beta has also been shown to suppress a protective immune response against M. bovis by promoting elimination of activated T cells 57 . Furthermore, previous studies in humans have identified higher levels of TGF-β production by circulating monocytes in tuberculosis patients and that this increase is a major contributor to depressed T cell functions in peripheral blood 58 59 .…”

Section: Discussionmentioning

confidence: 99%

The CD4+ T cell methylome contributes to a distinct CD4+ T cell transcriptional signature in Mycobacterium bovis-infected cattle

Doherty

Whiston

Cormican

et al. 2016

Sci Rep

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We hypothesised that epigenetic regulation of CD4+ T lymphocytes contributes to a shift toward a dysfunctional T cell phenotype which may impact on their ability to clear mycobacterial infection. Combined RNA-seq transcriptomic profiling and Reduced Representation Bisulfite Sequencing identified 193 significantly differentially expressed genes and 760 differentially methylated regions (DMRs), between CD4+ T cells from M. bovis infected and healthy cattle. 196 DMRs were located within 10 kb of annotated genes, including GATA3 and RORC, both of which encode transcription factors that promote TH2 and TH17 T helper cell subsets respectively. Gene-specific DNA methylation and gene expression levels for the TNFRSF4 and Interferon-γ genes were significantly negatively correlated suggesting a regulatory relationship. Pathway analysis of DMRs identified enrichment of genes involved in the anti-proliferative TGF-β signaling pathway and TGFB1 expression was significantly increased in peripheral blood leukocytes from TB-infected cattle. This first analysis of the bovine CD4+ T cell methylome suggests that DNA methylation directly contributes to a distinct gene expression signature in CD4+ T cells from cattle infected with M. bovis. Specific methylation changes proximal to key inflammatory gene loci may be critical to the emergence of a non-protective CD4+ T cell response during mycobacterial infection in cattle.

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Section: Discussionmentioning

confidence: 99%

The CD4+ T cell methylome contributes to a distinct CD4+ T cell transcriptional signature in Mycobacterium bovis-infected cattle

Doherty

Whiston

Cormican

et al. 2016

Sci Rep

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“…At least 3 mechanisms have been proposed. First, TGF-b increases the apoptosis of T cells activated by mycobacterial antigens [35][36][37]. Second, TGF-b enhances the growth of M. tuberculosis in macrophages [38], although not very effectively [39].…”

Section: Mechanisms Of Immunity To M Tuberculosismentioning

confidence: 99%

Immunotherapeutics for Tuberculosis in Experimental Animals: Is There a Common Pathway Activated by Effective Protocols?

Rook¹,

Lowrie²,

Hernández-Pando³

2007

J INFECT DIS

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The increasing threat posed by drug-resistant strains of M. tuberculosis is leading to a reappraisal of the possibility of treating tuberculosis (TB) by immunotherapy. We analyze 6 strategies that have been shown to be therapeutic in animal models of TB and identify a common pathway underlying the activity of the superficially different immunotherapeutic protocols. This pathway involves enhanced induction of CD8(+) cytotoxic T lymphocytes (CTLs) and down-regulation of interleukin-4 and transforming growth factor- beta , leading to further enhancement of the activity of CD8(+) CTLs and of other microbicidal pathways. This unifying analysis strengthens the rationale for future trials of immunotherapy in humans and points to surrogate markers that could be studied in such trials.

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“…Secretion of immunosuppressive cytokines such as TGF-beta (159) and IL10 (160) by macrophages may be one of the mechanisms in attenuating the immune response to M. tuberculosis infection and may be involved in reactivation of disease (161). In a recent study, TGF-beta was found to suppress the immune response by causing increased apoptosis in M. bovis activated CD4+ T cells (162). In a mouse model of Leishmania major persistence in the skin after healing in resistant mice C57BL/6, CD4+CD25+ regulatory T cells accumulated in the dermis were involved in maintaining the persistence by suppressing effector T cells by IL-10 dependent and IL-10 independent mechanisms (163).…”

Section: Immune Factorsmentioning

confidence: 99%

Persistent and dormant tubercle bacilli and latent tuberculosis

Zhang¹

2004

Front Biosci

176

139

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Tubercle bacillus has remarkable ability to persist in the human host and has caused latent infection in one third of the world population. The current tuberculosis (TB) chemotherapy while effective in killing growing bacilli is largely ineffective in killing persistent or dormant bacilli, leading to prolonged therapy. There is considerable recent interest to study mechanisms of persistence and dormancy in mycobacteria. Meanwhile, there is also confusion about the use of terminology of dormant and persistent bacilli. Different models of mycobacterial persistence have been established. Various mycobacterial factors have recently been identified that may be involved in persistence or dormancy and resuscitation of dormant organisms. The phenotypic resistance to antituberculosis drugs in persistent and dormant bacilli presents a major challenge for effective control of the disease. The host immune system is critical in controlling latent TB infection from reactivation. A recent interesting observation is the reactivation of latent TB infection by anti-TNF-alpha antibody used as a treatment for rheumatoid arthritis and Crohn's disease. The role of psychoneuroendocrinological factors in TB, which is often ignored in the era of modern chemotherapy but could be important for controlling latent infection, is also briefly reviewed. There is recent interest to develop new TB drugs that target persistent and dormant bacilli and also immunotherapeutic agents that enhance chemotherapy and better control latent infection. The complex interaction between the bacteria, drugs, host and the environment underscores the need for a combined approach that incorporates chemotherapy, immunotherapeutic agents, improved socioeconomic, nutritional and even conducive psychological factors for more effective control of TB and latent TB.

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Transforming Growth Factor-β Decreases Survival of Mycobacterium bovis-Activated T Cells

Cited by 9 publications

References 31 publications

The CD4+ T cell methylome contributes to a distinct CD4+ T cell transcriptional signature in Mycobacterium bovis-infected cattle

The CD4+ T cell methylome contributes to a distinct CD4+ T cell transcriptional signature in Mycobacterium bovis-infected cattle

Immunotherapeutics for Tuberculosis in Experimental Animals: Is There a Common Pathway Activated by Effective Protocols?

Persistent and dormant tubercle bacilli and latent tuberculosis

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