Evaluation of the overall IFN-γ and IL-17 pro-inflammatory responses after DNA therapy of tuberculosis

Zárate-Bladés, Carlos R.; Rodrigues, Raphaela Farias; Souza, Patrícia Jorge Soalheiro de; Rios, Wendy Martin; Soares, Luana Silva; Rosada, Rogério Silva; Brandão, I. T.; Masson, Ana Paula; Floriano, Elaine M.; Ramos, Simone G.; Silva, Célio Lopes

doi:10.4161/hv.23417

Cited by 13 publications

(13 citation statements)

References 64 publications

(87 reference statements)

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“…Although the CD4 + T cells are the most important players, the participation of MHC class I mediated CD8 + T cells in immunity to TB has been demonstrated . Modulation of the protective immune responses is known to be mediated through enhanced CD8 + T cell activity, producing IFN‐γ and an increasing γ/δ T cells . Antigen‐specific CD8 + T cells recognize and lyse MTB–infected cells and produce critical cytokines for macrophage activation (TNF‐α and IFN‐γ) , and the role of CD8 + cell is also supported by TAP deficient animal model research; disseminated infection in mice lacking HLA class I presentation pathways .…”

Section: Discussionmentioning

confidence: 99%

Association of TAP1 and TAP2 genes with susceptibility to pulmonary tuberculosis in Koreans

Roh

Yoon

Shin

et al. 2015

APMIS

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Tuberculosis remains an important public health problem in Koreans. However, very few studies have reported on the genetic factors associated with TB susceptibility in Koreans. The aim of this study was to elucidate the genetic factors associated with susceptibility to pulmonary tuberculosis (PTB). We investigated the transporter associated with antigen processing -1 (TAP1) and TAP2 gene polymorphisms in 160 Korean PTB patients (categorized according to extent of lesion and TB medication history) and 210 controls. TAP2*C/E frequency was significantly increased in the PTB (pc = 0.004, OR = 2.28). TAP2*Bky2/C/E were enriched in the retreated, far-advanced and total PTB compared with the controls (pc = 0.015, OR = 3.27; pc = 0.019, OR = 2.56; pc = 2.8 × 10(-4) , OR = 2.42, respectively). In the comparison of TAP2 gene with the DRB1*08:03, which is associated with TAP2*Bky2 and PTB in Koreans, we demonstrated the hierarchy of these association factors. TAP2*C/E is independent factors as strong as DRB1*08:03, and TAP2*C/E interacts with DRB1*08:03, resulting in a striking combined association. Our results suggest that TAP2 gene has an association with PTB susceptibility, the extent of the lesion or recurrence. These associations are independent from and additive with DRB1*08:03.

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Section: Discussionmentioning

confidence: 99%

Association of TAP1 and TAP2 genes with susceptibility to pulmonary tuberculosis in Koreans

Roh

Yoon

Shin

et al. 2015

APMIS

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“…DNA vaccines used directly or as prime-boost are alternative promising approaches to either improve the efficacy of the current BCG vaccine or to create a new more effective one (Rivas-Santiago and Cervantes-Villagrana, 2014). Plasmids containing M. tuberculosis DNA (from Ag85, Hsp65, and the 23 members of Esx gene family) used in experimental DNA vaccines have been found to lead to higher INF-g production and consequent induction of autophagy (Meerak et al, 2013;Zarate-Blades et al, 2013;Villarreal et al, 2014).…”

Section: Arg677trp (C2029t)mentioning

confidence: 99%

Autophagy in the Fight Against Tuberculosis

Bento

Empadinhas

Mendes

2015

DNA and Cell Biology

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Tuberculosis (TB), a chronic infectious disease mainly caused by the tubercle bacillus Mycobacterium tuberculosis, is one of the world's deadliest diseases that has afflicted humanity since ancient times. Although the number of people falling ill with TB each year is declining, its incidence in many developing countries is still a major cause of concern. Upon invading host cells by phagocytosis, M. tuberculosis can replicate within infected cells by arresting the maturation of the phagosome whose function is to target the pathogen for elimination. Host cells have mechanisms of controlling this evasion by inducing autophagy, an elaborate cellular process that targets bacteria for progressive elimination, decreasing bacterial loads within infected cells. In addition, autophagy activation also aids in the control of inflammation, contributing to a more efficient innate immune response against M. tuberculosis. Several innovative TB therapies have been envisaged based on autophagy manipulation, with some of them revealing high potential for future clinical trials and eventual implementation in healthcare systems. Thus, this review highlights the recent advances on the innate immune response regulation by autophagy upon M. tuberculosis infection and the promising new autophagy-based therapies for TB. Mycobacterium tuberculosis: Biology and Infection

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“…36 It is noteworthy that preclinical studies showed that protection induced by DNA-HSP65 immunization was dependent on upregulation of IFN-g levels, although this vaccine also had stimulated antigen-specific IL-10 production. 13,37 Our findings show that rHsp65 induced an increased secretion of IL-10 and DNA-Hsp65 stimulation resulted in an increase of IL-10-producing cells from healthy individuals and from TB patients.…”

Section: Discussionmentioning

confidence: 64%

Mycobacterial Hsp65 antigen upregulates the cellular immune response of healthy individuals compared with tuberculosis patients

Wowk

Franco

Fonseca

et al. 2017

Human Vaccines & Immunotherapeutics

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Previously we showed that 65-kDa Mycobacterium leprae heat shock protein (Hsp65) is a target for the development of a tuberculosis vaccine. Here we evaluated peripheral blood mononuclear cells (PBMC) from healthy individuals or tuberculosis patients stimulated with two forms of Hsp65 antigen, recombinant DNA that encodes Hsp65 (DNA-HSP65) or recombinant Hsp65 protein (rHsp65) in attempting to mimic a prophylactic or therapeutic study in vitro, respectively. Proliferation and cytokine-producing CD4 or CD8 cell were assessed by flow cytometry. The CD4 cell proliferation from healthy individuals was stimulated by DNA-HSP65 and rHsp65, while CD8 cell proliferation from healthy individuals or tuberculosis patients was stimulated by rHSP65. DNA-HSP65 did not improve the frequency of IFN-gamma cells from healthy individuals or tuberculosis patients. Furthermore, we found an increase in the frequency of IL-10-producing cells in both groups. These findings show that Hsp65 antigen activates human lymphocytes and plays an immune regulatory role that should be addressed as an additional antigen for the development of antigen-combined therapies.

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Evaluation of the overall IFN-γ and IL-17 pro-inflammatory responses after DNA therapy of tuberculosis

Cited by 13 publications

References 64 publications

Association of TAP1 and TAP2 genes with susceptibility to pulmonary tuberculosis in Koreans

Association of TAP1 and TAP2 genes with susceptibility to pulmonary tuberculosis in Koreans

Autophagy in the Fight Against Tuberculosis

Mycobacterial Hsp65 antigen upregulates the cellular immune response of healthy individuals compared with tuberculosis patients

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