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      An Overlooked and Underrated Endemic Mycosis—Talaromycosis and the Pathogenic Fungus Talaromyces marneffei

      1 , 2 , 1 , 3
      Clinical Microbiology Reviews
      American Society for Microbiology

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          Abstract

          Talaromycosis is an invasive mycosis endemic in tropical and subtropical Asia and is caused by the pathogenic fungus Talaromyces marneffei . Approximately 17,300 cases of T. marneffei infection are diagnosed annually, and the reported mortality rate is extremely high (~1/3).

          SUMMARY

          Talaromycosis is an invasive mycosis endemic in tropical and subtropical Asia and is caused by the pathogenic fungus Talaromyces marneffei . Approximately 17,300 cases of T. marneffei infection are diagnosed annually, and the reported mortality rate is extremely high (~1/3). Despite the devastating impact of talaromycosis on immunocompromised individuals, particularly HIV-positive persons, and the increase in reported occurrences in HIV-uninfected persons, diagnostic and therapeutic approaches for talaromycosis have received far too little attention worldwide. In 2021, scientists living in countries where talaromycosis is endemic raised a global demand for it to be recognized as a neglected tropical disease. Therefore, T. marneffei and the infectious disease induced by this fungus must be treated with concern. T. marneffei is a thermally dimorphic saprophytic fungus with a complicated mycological growth process that may produce various cell types in its life cycle, including conidia, hyphae, and yeast, all of which are associated with its pathogenicity. However, understanding of the pathogenic mechanism of T. marneffei has been limited until recently. To achieve a holistic view of T. marneffei and talaromycosis, the current knowledge about talaromycosis and research breakthroughs regarding T. marneffei growth biology are discussed in this review, along with the interaction of the fungus with environmental stimuli and the host immune response to fungal infection. Importantly, the future research directions required for understanding this serious infection and its causative pathogenic fungus are also emphasized to identify solutions that will alleviate the suffering of susceptible individuals worldwide.

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          Most cited references344

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          The NLRP3 inflammasome: molecular activation and regulation to therapeutics

          NLRP3 (NACHT, LRR and PYD domains-containing protein 3) is an intracellular sensor that detects a broad range of microbial motifs, endogenous danger signals and environmental irritants, resulting in the formation and activation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase-1-dependent release of the proinflammatory cytokines, IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. Recent studies have revealed new regulators of the NLRP3 inflammasome, including new interacting or regulatory proteins, metabolic pathways and a regulatory mitochondrial hub. In this Review, we present the molecular, cell biological and biochemical basis of NLRP3 activation and regulation, and describe how this mechanistic understanding is leading to potential therapeutics that target the NLRP3 inflammasome.
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            The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation

            The NLRP3 inflammasome is a critical component of the innate immune system that mediates caspase-1 activation and the secretion of proinflammatory cytokines IL-1β/IL-18 in response to microbial infection and cellular damage. However, the aberrant activation of the NLRP3 inflammasome has been linked with several inflammatory disorders, which include cryopyrin-associated periodic syndromes, Alzheimer’s disease, diabetes, and atherosclerosis. The NLRP3 inflammasome is activated by diverse stimuli, and multiple molecular and cellular events, including ionic flux, mitochondrial dysfunction, and the production of reactive oxygen species, and lysosomal damage have been shown to trigger its activation. How NLRP3 responds to those signaling events and initiates the assembly of the NLRP3 inflammasome is not fully understood. In this review, we summarize our current understanding of the mechanisms of NLRP3 inflammasome activation by multiple signaling events, and its regulation by post-translational modifications and interacting partners of NLRP3.
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              The M1 and M2 paradigm of macrophage activation: time for reassessment

              Macrophages are endowed with a variety of receptors for lineage-determining growth factors, T helper (Th) cell cytokines, and B cell, host, and microbial products. In tissues, macrophages mature and are activated in a dynamic response to combinations of these stimuli to acquire specialized functional phenotypes. As for the lymphocyte system, a dichotomy has been proposed for macrophage activation: classic vs. alternative, also M1 and M2, respectively. In view of recent research about macrophage functions and the increasing number of immune-relevant ligands, a revision of the model is needed. Here, we assess how cytokines and pathogen signals influence their functional phenotypes and the evidence for M1 and M2 functions and revisit a paradigm initially based on the role of a restricted set of selected ligands in the immune response.
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                Author and article information

                Contributors
                Journal
                Clinical Microbiology Reviews
                Clin Microbiol Rev
                American Society for Microbiology
                0893-8512
                1098-6618
                March 23 2023
                March 23 2023
                : 36
                : 1
                Affiliations
                [1 ]Intensive Care Unit, Biomedical Research Center, Shenzhen Institute of Translational Medicine, Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, China
                [2 ]Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada
                [3 ]Department of Burn and Plastic Surgery, Biomedical Research Center, Shenzhen Institute of Translational Medicine, Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, China
                Article
                10.1128/cmr.00051-22
                36648228
                7f4ef5c0-180e-429a-8092-2ed78d122d51
                © 2023

                https://doi.org/10.1128/ASMCopyrightv2

                https://journals.asm.org/non-commercial-tdm-license

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