scholarly journals Exposure of Monocytes to Lipoarabinomannan Promotes Their Differentiation into Functionally and Phenotypically Immature Macrophages

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Leslie Chávez-Galán ◽  
Ranferi Ocaña-Guzmán ◽  
Luis Torre-Bouscoulet ◽  
Carolina García-de-Alba ◽  
Isabel Sada-Ovalle
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Etiologic Agent ◽  
Human Monocytes ◽  
Adaptive Immune Responses ◽  
Phagocytic Capacity ◽  
Monocyte Differentiation ◽  
Tuberculosis Patients ◽  
Adaptive Immune

Lipoarabinomannan (LAM) is a lipid virulence factor secreted byMycobacterium tuberculosis(Mtb), the etiologic agent of tuberculosis. LAM can be measured in the urine or serum of tuberculosis patients (TB-patients). Circulating monocytes are the precursor cells of alveolar macrophages and might be exposed to LAM in patients with active TB. We speculated that exposing monocytes to LAM could produce phenotypically and functionally immature macrophages. To test our hypothesis, human monocytes were stimulated with LAM (24–120 hours) and various readouts were measured. The study showed that when monocytes were exposed to LAM, the frequency of CD68+, CD33+, and CD86+macrophages decreased, suggesting that monocyte differentiation into mature macrophages was affected. Regarding functionality markers, TLR2+and TLR4+macrophages also decreased, but the percentage of MMR+expression did not change. LAM-exposed monocytes generated macrophages that were less efficient in producing proinflammatory cytokines such as TNF-αand IFN-γ; however, their phagocytic capacity was not modified. Taken together, these data indicate that LAM exposure influenced monocyte differentiation and produced poorly functional macrophages with a different phenotype. These results may help us understand how mycobacteria can limit the quality of the innate and adaptive immune responses.

scholarly journals Lessons from Bacillus Calmette-Guérin: Harnessing Trained Immunity for Vaccine Development

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2109
Author(s):  
Samuel T. Pasco ◽  
Juan Anguita
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Vaccine Development ◽  
Vaccine Design ◽  
Innate Immune ◽  
Bacillus Calmette Guerin ◽  
Adaptive Immune Responses ◽  
Trained Immunity ◽  
Adaptive Immune ◽  
Potential Methods

Vaccine design traditionally focuses on inducing adaptive immune responses against a sole target pathogen. Considering that many microbes evade innate immune mechanisms to initiate infection, and in light of the discovery of epigenetically mediated innate immune training, the paradigm of vaccine design has the potential to change. The Bacillus Calmette-Guérin (BCG) vaccine induces some level of protection against Mycobacterium tuberculosis (Mtb) while stimulating trained immunity that correlates with lower mortality and increased protection against unrelated pathogens. This review will explore BCG-induced trained immunity, including the required pathways to establish this phenotype. Additionally, potential methods to improve or expand BCG trained immunity effects through alternative vaccine delivery and formulation methods will be discussed. Finally, advances in new anti-Mtb vaccines, other antimicrobial uses for BCG, and “innate memory-based vaccines” will be examined.

scholarly journals Mycobacterium tuberculosis PE_PGRS20 and PE_PGRS47 Proteins Inhibit Autophagy by Interaction with Rab1A

mSphere ◽  
2021 ◽  
Author(s):  
Emily J. Strong ◽  
Tony W. Ng ◽  
Steven A. Porcelli ◽  
Sunhee Lee
Keyword(s):  
Infectious Disease ◽  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Cellular Process ◽  
Phagocytic Cells ◽  
Adaptive Immune Responses ◽  
Content Type ◽  
Adaptive Immune ◽  
Intracellular Infections

Tuberculosis is a significant global infectious disease caused by infection of the lungs with Mycobacterium tuberculosis , which then resides and replicates mainly within host phagocytic cells. Autophagy is a complex host cellular process that helps control intracellular infections and enhance innate and adaptive immune responses.

scholarly journals Subunit Vaccine ESAT-6:c-di-AMP Delivered by Intranasal Route Elicits Immune Responses and Protects Against Mycobacterium tuberculosis Infection

2021 ◽  
Vol 11 ◽  
Author(s):  
Huanhuan Ning ◽  
Wei Zhang ◽  
Jian Kang ◽  
Tianbing Ding ◽  
Xuan Liang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Subunit Vaccine ◽  
Mucosal Vaccine ◽  
Intranasal Route ◽  
Mycobacterium Tuberculosis Infection ◽  
Adaptive Immune Responses ◽  
Common Cause ◽  
Adaptive Immune ◽  
A Subunit

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, remains the most common cause of death from a single infectious disease. More safe and effective vaccines are necessary for preventing the prevalence of TB. In this study, a subunit vaccine of ESAT-6 formulated with c-di-AMP (ESAT-6:c-di-AMP) promoted mucosal and systemic immune responses in spleen and lung. ESAT-6:c-di-AMP inhibited the differentiations of CD8+ T cells as well as macrophages, but promoted the differentiations of ILCs in lung. The co-stimulation also enhanced inflammatory cytokines production in MH-S cells. It was first revealed that ESAT-6 and c-di-AMP regulated autophagy of macrophages in different stages, which together resulted in the inhibition of Mtb growth in macrophages during early infection. After Mtb infection, the level of ESAT-6-specific immune responses induced by ESAT-6:c-di-AMP dropped sharply. Finally, inoculation of ESAT-6:c-di-AMP led to significant reduction of bacterial burdens in lungs and spleens of immunized mice. Our results demonstrated that subunit vaccine ESAT-6:c-di-AMP could elicit innate and adaptive immune responses which provided protection against Mtb challenge, and c-di-AMP as a mucosal adjuvant could enhance immunogenicity of antigen, especially for innate immunity, which might be used for new mucosal vaccine against TB.

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