Immunomodulation as Therapy for Fungal Infection: Are We Closer?

Sam, Qi Hui; Yew, Wen Shan; Seneviratne, Chaminda Jayampath; Chang, Matthew Wook; Chai, Louis Yi Ann

doi:10.3389/fmicb.2018.01612

Cited by 46 publications

(38 citation statements)

References 136 publications

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“…The incidence and mortality of Candida sepsis remain high (Wenzel and Gennings, 2005;Pappas et al, 2016). Consequently, a lot of research has attempted to address this problem by immunoregulation or enhancing host immunity (Delsing et al, 2014;Sam et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

T-Bet Expression Mediated by the mTOR Pathway Influences CD4+ T Cell Count in Mice With Lethal Candida Sepsis

et al. 2020

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The sustained high morbidity and mortality of Candida sepsis are mainly caused by compromise of host immunity. Clinically, it is often manifested as a significant decrease in CD4 + T cell count, although the mechanism is unclear. We established a lethal mice Candida sepsis model and used Murine Sepsis Score to group mice with different disease severity to establish the influence of T-bet expression on CD4 + T cell count in Candida sepsis. We found that CD4 + T cell count decreased in Candida-infected compared to uninfected mice, and the degree of decrease increased with aggravation of sepsis. Expression of T-bet similarly decreased with worsening of sepsis, but it was significantly enhanced in candidiasis in comparison of naïve state. To clarify its possible mechanism, we measured the activity of mammalian target of rapamycin (mTOR), which is a key regulator of T-bet expression. The mTOR pathway was activated after infection and its activity increased with progression of sepsis. We used mice with T-cell-specific knockout of mTOR or tuberous sclerosis complex (TSC)1 to further inhibit or strengthen the mTOR signaling pathway. We found that mTOR deletion mice had a higher CD4 + T cell count by regulating T-bet expression, and the result in TSC1 deletion mice was reversed. These results demonstrate that T-bet expression mediated by the mTOR pathway influences the CD4 + T cell count in mice with Candida sepsis.

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Section: Introductionmentioning

confidence: 99%

T-Bet Expression Mediated by the mTOR Pathway Influences CD4+ T Cell Count in Mice With Lethal Candida Sepsis

et al. 2020

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“…It is commonly used in cancer therapy and is a candidate for antifungal immunotherapy or immunization. [75][76][77] We have developed a DC vaccine against cryptococcosis caused by highly virulent C. gattii. 14) In this approach, DCs were pulsed with the heat-inactivated C. gattii acapsular mutant ∆cap60, and then the antigen-pulsed DCs were transferred to the host.…”

Section: Adjuvants and Actmentioning

confidence: 99%

Vaccines and Protective Immune Memory against Cryptococcosis

Ueno

Yanagihara

Shimizu

et al. 2020

Biological & Pharmaceutical Bulletin

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Cryptococcosis is a potentially lethal disease caused by fungal pathogens including Cryptococcus neoformans and Cryptococcus gattii species complex. These fungal pathogens live in the environment and are associated with certain tree species and bird droppings. This infectious disease is not contagious, and healthy individuals may contract cryptococcal infections by inhaling the airborne pathogens from the environment. Although cleaning a contaminated environment is a feasible approach to control environmental fungal pathogens, prophylactic immunization is also considered a promising method to regulate cryptococcal infections. We review the history of the development of cryptococcal vaccines, vaccine components, and the various forms of immune memory induced by cryptococcal vaccines.

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“…Immunomodulatory therapy aims to augment or correct the compromised immune function instead of directly killing pathogens, and the strategy was well elucidated by Qi Hui Sam et al in the case of fungal infections. Herein, we discuss some medications that are promising in cryptococcosis.…”

Section: Adjunctive Therapymentioning

confidence: 99%

Management of human immunodeficiency virus–associated cryptococcal meningitis: Current status and future directions

Shen

2019

Mycoses

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Summary Cryptococcal meningitis (CM) is one of the most common opportunistic infections of acquired immunodeficiency syndrome (AIDS), as well as an important cause of hospitalisation and death. In recent years, the mortality of CM has remained high in HIV/AIDS population, with up to 30%, including within developed countries. The treatment usually encompasses controls of Cryptococcus, HIV, and increased intracranial pressure. Recent progress on the management of HIV‐associated CM mainly centres in optimising induction regimens, looking for appropriate timing of initiating antiretroviral therapy and prevention of symptomatic onset and adverse consequences. This review compared several international guidelines combined with the results from some clinical researches to illustrate the similarities, differences and potential in CM treatment. The present practice is still far from satisfactory, and there remains much to explore due to our limited understanding of the pathogenesis of HIV‐associated CM. Thus, screening and monitoring should be strengthened, and better therapies in line with the actual situation of each country should be discovered.

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Immunomodulation as Therapy for Fungal Infection: Are We Closer?

Cited by 46 publications

References 136 publications

T-Bet Expression Mediated by the mTOR Pathway Influences CD4+ T Cell Count in Mice With Lethal Candida Sepsis

T-Bet Expression Mediated by the mTOR Pathway Influences CD4+ T Cell Count in Mice With Lethal Candida Sepsis

Vaccines and Protective Immune Memory against Cryptococcosis

Management of human immunodeficiency virus–associated cryptococcal meningitis: Current status and future directions

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