Toll-like receptors in mycobacterial infection

Vu, Ann; Calzadilla, Andrew; Gidfar, Sanaz; Candelario, R.A. Calderon; Mirsaeidi, Mehdi

doi:10.1016/j.ejphar.2016.10.018

Cited by 22 publications

(15 citation statements)

References 75 publications

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“…The toll-like receptors (TLRs) are widely studied and found in the antigen-presenting cells (APCs). 58 With the interaction of vaccines and this receptor, it is possible to be certain that the vaccinal antigen will be recognized by the APC-specific receptors and these, after activation, will promote immune, innate responses and activate the adaptive immune response. Therefore, in this study, the hydrophobic areas of the CP40 protein and their respective immunodominant epitopes interact with TLR2, which plays an important role in the activation of the immune response.…”

Section: Discussionmentioning

confidence: 99%

Immune-Informatic Analysis and Design of Peptide Vaccine From Multi-epitopes Against Corynebacterium pseudotuberculosis

Droppa-Almeida

Franceschi

Padilha

2018

Bioinform Biol Insights

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Caseous lymphadenitis (CLA) is a disease caused by Corynebacterium pseudotuberculosis bacteria that affects sheep and goats. The absence of a serologic diagnose is a factor that contributes for the disease dissemination, and due to the formation of granuloma, the treatment is very expensive. Therefore, prophylaxis is the approach with best cost-benefit relation; however, it still lacks an effective vaccine. In this sense, this work seeks to apply bioinformatic tools to design an effective vaccine against CLA, using CP40 protein as standard for the design of immunodominant epitopes, from which a total of 6 sequences were obtained, varying from 10 to 16 amino acid residues. The evaluation of different properties of the vaccines showed that the vaccine is a potent and nonallergenic antigen remaining stable in a wide range of temperatures. The initial tertiary structure of the vaccine was then predicted and a model selected. Later, the process of CP40 protein and TLR2 receptor binding was performed, presenting interaction with this receptor, which plays an important role in the activation of the immune response.

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Section: Discussionmentioning

confidence: 99%

Immune-Informatic Analysis and Design of Peptide Vaccine From Multi-epitopes Against Corynebacterium pseudotuberculosis

Droppa-Almeida

Franceschi

Padilha

2018

Bioinform Biol Insights

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“…5,6 The binding of TLRs with their corresponding ligands leads to recruitment of adaptor proteins, activation of downstream signal transduction pathways, up-regulation of cytokine and chemokine production, and ultimately the development of immune responses against exogenous pathogens. 7,8 Consequently, it is possible that TLR gene polymorphisms, which may impact biological activities of TLRs, might also be involved in the development of multiple infectious diseases, including TB. 9 To date, numerous studies have already investigated potential associations between TLR gene polymorphisms and TB.…”

Section: Introductionmentioning

confidence: 99%

Associations between genetic polymorphisms of TLRs and susceptibility to tuberculosis: A meta-analysis

Zhou¹,

Zhang

2019

Innate Immun

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Some genetic association studies have tried to investigate potential associations between TLR polymorphisms and tuberculosis. However, the results of these studies have not been consistent. Thus, we performed the present meta-analysis to explore associations between TLR polymorphisms and tuberculosis in a larger combined population. A systematic literature research of PubMed, Web of Science and Embase was performed to identify eligible studies for combined analyses. I2 statistics were employed to assess between-study heterogeneities. If I2 was >50%, random-effects models were used to combine the data. Otherwise, fixed-effects models were applied for synthetic analyses. A total of 39 genetic association studies were included in the analyses. The combined analyses showed that TLR1 rs4833095, TLR1 rs5743557, TLR1 rs5743596, TLR2 rs3804099, TLR2 rs5743704, TLR2 rs5743708, TLR6 rs5743810 and TLR8 rs3764879 polymorphisms were significantly associated with susceptibility to TB in the overall population. Further subgroup analyses revealed similar significant findings for TLR1 rs4833095, TLR1 rs5743557, TLR1 rs5743596, TLR1 rs5743618, TLR2 rs3804099, TLR2 rs5743704, TLR2 rs5743708, TLR4 rs4986790 and TLR4 rs4986791 polymorphisms in certain ethnicities. In conclusion, our findings support that these TLR polymorphisms may be used to identify individuals at high risk of developing tuberculosis.

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“…Among these PRRs, toll-like receptors (TLRs) are the most important members expressed on the surface of DCs. Mammalian TLRs consist of 13 members, and TLR4 is the first member discovered and has been proved to induce the activation and expression of NF-κB, which controls the genes for the inflammatory cytokines [ 23 ]. Recent researches have showed that the specific immune responses caused by helminth infections were closely related with TLRs, and TLR2 and TLR4 are most frequently involved [ 24 – 26 ].…”

Section: Introductionmentioning

confidence: 99%

Ts-Hsp70 induces protective immunity against Trichinella spiralis infection in mouse by activating dendritic cells through TLR2 and TLR4

et al. 2018

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BackgroundTrichinellosis is a serious food-borne parasitic zoonosis worldwide. In the effort to develop vaccine against Trichinella infection, we have identified Trichinella spiralis Heat shock protein 70 (Ts-Hsp70) elicits partial protective immunity against T. spiralis infection via activating dendritic cells (DCs) in our previous study. This study aims to investigate whether DCs were activated by Ts-Hsp70 through TLR2 and/or TLR4 pathways.Methods and findingsAfter blocking with anti-TLR2 and TLR4 antibodies, the binding of Ts-Hsp70 to DCs was significantly reduced. The reduced binding effects were also found in TLR2 and TLR4 knockout (TLR2-/- and TLR4-/-) DCs. The expression of TLR2 and TLR4 on DCs was upregulated after treatment with Ts-Hsp70 in vitro. These results suggest that Ts-Hsp70 is able to directly bind to TLR2 and TLR4 on the surface of mouse bone morrow-derived DCs. In addition, the expression of the co-stimulatory molecules (CD80, CD83) on Ts-Hsp70-induced DCs was reduced in TLR2-/- and TLR4-/- mice. More evidence showed that Ts-Hsp70 reduced its activation on TLR2/4 knockout DCs to subsequently activate the naïve T-cells. Furthermore, Ts-Hsp70 elicited protective immunity against T. spiralis infection was reduced in TLR2-/- and TLR4-/- mice correlating with the reduced humoral and cellular immune responses.ConclusionThis study demonstrates that Ts-Hsp70 activates DCs through TLR2 and TLR4, and TLR2 and TLR4 play important roles in Ts-Hsp70-induced DCs activation and immune responses.

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Toll-like receptors in mycobacterial infection

Cited by 22 publications

References 75 publications

Immune-Informatic Analysis and Design of Peptide Vaccine From Multi-epitopes Against Corynebacterium pseudotuberculosis

Immune-Informatic Analysis and Design of Peptide Vaccine From Multi-epitopes Against Corynebacterium pseudotuberculosis

Associations between genetic polymorphisms of TLRs and susceptibility to tuberculosis: A meta-analysis

Ts-Hsp70 induces protective immunity against Trichinella spiralis infection in mouse by activating dendritic cells through TLR2 and TLR4

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