The preventable efficacy of β-glucan against leptospirosis

Wang, Jiaqi; Zhao, Jin; Zhang, Wenlong; Xie, Xufeng; Song, Ning; Lv, Tianbao; Wu, Di; Cao, Yongguo

doi:10.1371/journal.pntd.0007789

Cited by 13 publications

(19 citation statements)

References 45 publications

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“…Its downregulation in the macrophages coming from β-glucan-treated dogs is another evidence toward trained immunity implementation in vivo . Comparable induction of pro-inflammatory profiles of macrophages by immune training has been reported in a context of protection against leptospirosis in hamster, highlighting the clinical use of trained immunity in pathogen-related diseases ( 24 ).…”

Section: Discussionmentioning

confidence: 84%

β-Glucan as Trained Immunity-Based Adjuvants for Rabies Vaccines in Dogs

et al. 2020

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The mechanisms of trained immunity have been extensively described in vitro and the beneficial effects are starting to be deciphered in in vivo settings. Prototypical compounds inducing trained immunity, such as β-glucans, act through epigenetic reprogramming and metabolic changes of innate immune cells. The recent advances in this field have opened new areas for the development of Trained immunity-based adjuvants (TIbAs). In this study, we assessed in dogs the potential immune training effects of β-glucans as well as their capacity to enhance the adaptive immune response of an inactivated rabies vaccine (Rabisin ® ). Injection of β-glucan from Euglena gracilis was performed 1 month before vaccination with Rabisin ® supplemented or not with the same β-glucan used as adjuvant. Trained innate immunity parameters were assessed during the first month of the trial. The second phase of the study was focused on the ability of β-glucan to enhance adaptive immune responses measured by multiple immunological parameters. B and T-cell specific responses were monitored to evaluate the immunogenicity of the rabies vaccine adjuvanted with β-glucan or not. Our preliminary results support that adjuvantation of Rabisin ® vaccine with β-glucan elicit a higher B-lymphocyte immune response, the prevailing factor of protection against rabies. β-glucan also tend to stimulate the T cell response as shown by the cytokine secretion profile of PBMCs re-stimulated ex vivo. Our data are providing new insights on the impact of trained immunity on the adaptive immune response to vaccines in dogs. The administration of β-glucan, 1 month before or simultaneously to Rabisin ® vaccination give promising results for the generation of new TIbA candidates and their potential to provide increased immunogenicity of specific vaccines.

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Section: Discussionmentioning

confidence: 84%

β-Glucan as Trained Immunity-Based Adjuvants for Rabies Vaccines in Dogs

et al. 2020

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“… Enhancement of the immune system to better control leptospires. (A) Coinjection at the time of leptospiral infection of PRR agonists such as Pam3CSK (a TLR2 agonist) ( 138 ), β-glucan (a Dectin-1 agonist that potentially synergizes with TLR2) ( 139 ), or crude Escherichia coli LPS (a TLR2/TLR4 agonist) ( 126 ) leads to enhancement of hamster immune responses along with improved survival or delayed lethality and reductions in the number of survivors in tissue lesions, bacterial loads, and inflammation. (B) Recently, innate immune memory or trained immunity has been explored as a therapeutic strategy against leptospires.…”

Section: Part Iii—tlr/nlr Agonists Boost Phagocytic Responses Againstmentioning

confidence: 99%

“…Overall, this effect lasts for at least 3 months posttreatment, and ex vivo data suggest that it could be used to alleviate human leptospirosis. Another study used β-glucan ( 139 ), a main component of the fungal cell wall, to treat hamsters 5 days before infection. β-glucan pretreatment leads to reduced mortality and decreased bacterial burden in blood and target organs as well as a reduction in tissue lesions and inflammation ( 139 ).…”

Section: Part Iii—tlr/nlr Agonists Boost Phagocytic Responses Againstmentioning

confidence: 99%

“…However, in vivo pharmacological inhibition of NO did not impact the outcome due to LPS ( 119 ), suggesting that the enhanced or restored MPO activity (or activity of other mediators) could be responsible for protection. Interestingly, coinjections starting 1 day prior to the time of leptospiral infection with ß-glucan, a fungal cell wall component agonist of the Dectin-1 receptor known to synergize with TLR2, also increased early inflammation and improved survival ( 139 ).…”

Section: Part Iii—tlr/nlr Agonists Boost Phagocytic Responses Againstmentioning

confidence: 99%

“…In addition, CL429 also triggered a trained immunity effect in human MΦ derived from monocytes of healthy blood donors ( 17 ). A recent study showed that ß-glucan, the prototypic MAMP used to induce trained immunity, was consistently effective in preventing severe leptospirosis in hamsters when administered 5 days prior to infection with L. interrogans serovar Lai strain 56601 ( 139 ) ( Figure 5 ). ß-glucan protected 37.5% of hamsters from death and alleviated lesions in the liver, lungs, and kidneys ( 139 ).…”

Section: Part Iii—tlr/nlr Agonists Boost Phagocytic Responses Againstmentioning

confidence: 99%

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Phagocyte Escape of Leptospira: The Role of TLRs and NLRs

et al. 2020

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The spirochetal bacteria Leptospira spp. are causative agents of leptospirosis, a globally neglected and reemerging zoonotic disease. Infection with these pathogens may lead to an acute and potentially fatal disease but also to chronic asymptomatic renal colonization. Both forms of disease demonstrate the ability of leptospires to evade the immune response of their hosts. In this review, we aim first to recapitulate the knowledge and explore the controversial data about the opsonization, recognition, intracellular survival, and killing of leptospires by scavenger cells, including platelets, neutrophils, macrophages, and dendritic cells. Second, we will summarize the known specificities of the recognition or escape of leptospire components (the so-called microbial-associated molecular patterns; MAMPs) by the pattern recognition receptors (PRRs) of the Toll-like and NOD-like families. These PRRs are expressed by phagocytes, and their stimulation by MAMPs triggers pro-inflammatory cytokine and chemokine production and bactericidal responses, such as antimicrobial peptide secretion and reactive oxygen species production. Finally, we will highlight recent studies suggesting that boosting or restoring phagocytic functions by treatments using agonists of the Toll-like or NOD receptors represents a novel prophylactic strategy and describe other potential therapeutic or vaccine strategies to combat leptospirosis.

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