Mycobacterium smegmatis proteoliposome induce protection in a murine progressive pulmonary tuberculosis model

Tirado, Yanely; Puig, Alina; Álvarez, Nadine; Borrero, Reinier; Aguilar, Alicia; Camacho, Frank; Reyes, Fátima; Fernández, Sonsire; Pérez, José Luís; Acevedo, Reynaldo; Espinoza, Dulce Mata; Payán, Jorge Alberto Barrios; García, María de los Ángeles Olivares; Kadir, Ramlah; Sarmiento, María E.; Hernández-Pando, Rogelio; Nor, Norazmi Mohd; Acosta, Armando

doi:10.1016/j.tube.2016.07.017

Cited by 11 publications

(9 citation statements)

References 29 publications

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“…The immunization with these proteins emulsified with IFA induced the secretion of protective Th1 cytokine (IFN-γ) from spleen cells and also lowered the bacterial load significantly in lungs [40]. Alum salts are known to be Th2-inducing adjuvants, however due to their safety and function of increasing the stability and immunogenicity of recombinant proteins, they have been widely used in pursuit of developing subunit TB vaccines and to compare new adjuvants [41][42][43][44][45]. Despite the positive correlation between the induction of high Th1 responses and protection against TB in mice, it has been shown that the use of Th2 inducing adjuvants, such as Alum, is not associated with harmful effects [46].…”

Section: Discussionmentioning

confidence: 99%

“…Orr and colleagues have shown that Alum in combination with glucopyranosyl lipid adjuvant (GLA) had a synergetic effect, promoted Th1 responses to ID93, and significantly reduced the bacterial load in the lungs and spleens of M. tuberculosisinfected mice [48]. On the other hand, Agger et al showed that combining Ag85B-ESXA fusion protein with Alum and dimethyldioctadecylammonium (DDA) adjuvants did not reduce the bacterial load in lungs of infected mice [42,46]. Besides, immunization of mice with the chimeric tuberculosis vaccine antigen H56 along with alum did not induce the secretion of primary T cell responses, rather it increased the primary B cell responses and IgG1 production [26].…”

Section: Discussionmentioning

confidence: 99%

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The effect of adjuvants and delivery systems on Th1, Th2, Th17 and Treg cytokine responses in mice immunized with Mycobacterium tuberculosis-specific proteins

Mustafa

Amoudy

et al. 2020

PLoS ONE

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Tuberculosis (TB) is a major health problem of global concern. The control of this disease requires appropriate preventive measures, including vaccines. In TB, T helper (Th)1 cytokines provide protection whereas Th2 and T regulatory (Treg) cytokines contribute to the pathogenesis and Th17 cytokines play a role in both protection and pathogenesis. Previous studies with Mycobacterium tuberculosis-specific proteins have identified seven low molecular weight proteins, PE35, ESXA, ESXB, Rv2346c, Rv2347c, Rv3619c, and Rv3620c, as immunodominant antigens inducing Th1-cell responses in humans following natural infection with M. tuberculosis. The aim of this study was to characterize the cytokine responses induced in mice immunized with these proteins, using various adjuvants and delivery systems, i.e. chemical adjuvants (Alum and IFA), non-pathogenic mycobacteria (M. smegmatis and M. vaccae) and a DNA vaccine plasmid (pUMVC6). The immune responses were monitored by quantifying the marker cytokines secreted by Th1 (IFN-γ), Th2 (IL-5), Treg (IL-10), and Th17 (IL-17A) cells. DNA corresponding to pe35, esxa, esxb, rv2346c, rv2347c, rv3619c, and rv3620c genes were cloned into the expression vectors pGES-TH-1, pDE22 and pUMVC6 for expression in Escherichia coli, mycobacteria and eukaryotic cells, respectively. Mice were immunized with the recombinants using different adjuvants and delivery systems, and spleen cells were stimulated in vitro with peptides of immunizing proteins to investigate antigen-specific secretion of Th1 (IFN-γ), Th2 (IL-5), Treg (IL-10), and Th17 (IL-17A) cytokines. The results showed that spleen cells, from mice immunized with all antigens, secreted the protective Th1 cytokine IFN-γ, except ESXB, with one or more adjuvants and delivery systems. However, only Rv3619c consistently induced Th1-biased responses, without the secretion of significant concentrations of Th2, Th17 and Treg cytokines, with all adjuvants and delivery systems. Rv3619c also induced antigen-specific IgG antibodies in immunized mice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The effect of adjuvants and delivery systems on Th1, Th2, Th17 and Treg cytokine responses in mice immunized with Mycobacterium tuberculosis-specific proteins

Mustafa

Amoudy

et al. 2020

PLoS ONE

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“…The antigenic similarity and immune cross-reactivity between mycobacteria have been exploited in the development of vaccines and immunotherapy of TB [17-19, 27, 203-211, 331-334]. Proteoliposomes [263] and lipid-based preparations of the cell envelope, obtained from M. smegmatis [264], were protective against Mtb intratracheal challenge in mice, and induced cross-reactive humoral immune responses against Mtb antigens [87,265,266].…”

Section: (A) Pathogen-related Prophylactic Measures: Blocking the Tramentioning

confidence: 99%

Pulmonary non-tuberculous mycobacterial infections: current state and future management

Chin

Sarmiento

Alvarez-Cabrera

et al. 2019

Eur J Clin Microbiol Infect Dis

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Currently, there is a trend of increasing incidence in pulmonary non-tuberculous mycobacterial infections (PNTM) together with a decrease in tuberculosis (TB) incidence, particularly in developed countries. The prevalence of PNTM in underdeveloped and developing countries remains unclear as there is still a lack of detection methods that could clearly diagnose PNTM applicable in these low-resource settings. Since non-tuberculous mycobacteria (NTM) are environmental pathogens, the vicinity favouring host-pathogen interactions is known as important predisposing factor for PNTM. The ongoing changes in world population, as well as socio-political and economic factors, are linked to the rise in the incidence of PNTM. Development is an important factor for the improvement of population well-being, but it has also been linked, in general, to detrimental environmental consequences, including the rise of emergent (usually neglected) infectious diseases, such as PNTM. The rise of neglected PNTM infections requires the expansion of the current efforts on the development of diagnostics, therapies and vaccines for mycobacterial diseases, which at present, are mainly focused on TB. This review discuss the current situation of PNTM and its predisposing factors, as well as the efforts and challenges for their control.

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“…In addition, it is important that this species shares more than 2000 homologous genes with M. tuberculosis and shares the same peculiar cell wall structure of M. tuberculosis and other mycobacterial species [29]. Thus, it is often used as a surrogate model for many TB studies [30][31][32]. Therefore, M. smegmatis was selected as the experimental strain in this experiment.…”

Section: Introductionmentioning

confidence: 99%

A synergistic bactericidal effect of low-frequency and low-intensity ultrasound combined with levofloxacin-loaded PLGA nanoparticles on M. smegmatis in macrophages

Xie

Hou

et al. 2020

J Nanobiotechnol

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Purpose: Tuberculosis (TB) is a highly infectious disease caused by Mycobacterium tuberculosis (Mtb), which often parasites in macrophages. This study is performed to investigate the bactericidal effect and underlying mechanisms of low-frequency and low-intensity ultrasound (LFLIU) combined with levofloxacin-loaded PLGA nanoparticles (LEV-NPs) on M. smegmatis (a surrogate of Mtb) in macrophages. Methods and results: The LEV-NPs were prepared using a double emulsification method. The average diameter, zeta potential, polydispersity index, morphology, and drug release efficiency in vitro of the LEV-NPs were investigated. M. smegmatis in macrophages was treated using the LEV-NPs combined with 42 kHz ultrasound irradiation at an intensity of 0.13 W/cm 2 for 10 min. The results showed that ultrasound significantly promoted the phagocytosis of nanoparticles by macrophages (P < 0.05). In addition, further ultrasound combined with the LEV-NPs promoted the production of reactive oxygen species (ROS) in macrophage, and the apoptosis rate of the macrophages was significantly higher than that of the control (P < 0.05). The transmission electronic microscope showed that the cell wall of M. smegmatis was ruptured, the cell structure was incomplete, and the bacteria received severe damage in the ultrasound combined with the LEV-NPs group. Activity assays showed that ultrasound combined with the LEV-NPs exhibited a tenfold higher antibacterial activity against M. smegmatis residing inside macrophages compared with the free drug. Conclusion: These data demonstrated that ultrasound combined with LEV-NPs has great potential as a therapeutic agent for TB.

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Mycobacterium smegmatis proteoliposome induce protection in a murine progressive pulmonary tuberculosis model

Cited by 11 publications

References 29 publications

The effect of adjuvants and delivery systems on Th1, Th2, Th17 and Treg cytokine responses in mice immunized with Mycobacterium tuberculosis-specific proteins

The effect of adjuvants and delivery systems on Th1, Th2, Th17 and Treg cytokine responses in mice immunized with Mycobacterium tuberculosis-specific proteins

Pulmonary non-tuberculous mycobacterial infections: current state and future management

A synergistic bactericidal effect of low-frequency and low-intensity ultrasound combined with levofloxacin-loaded PLGA nanoparticles on M. smegmatis in macrophages

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