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Penicillium marneffei is a significant pathogen of AIDS patients in Southeast Asia. This fungus is unique in that it is the only dimorphic member of the genus. Pathogenesis of P. marneffei requires the saprobic mold form to undergo a morphological change upon tissue invasion. The in vivo form of this fungus reproduces as a fission yeast that capabl...
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Context 1
... newly formed arthroconidia then grow as yeast- like cells that undergo brief elongation prior to septum formation and fission. Eventually, such growth establishes a nearly homogeneous culture of uninucleate yeast cells that are strikingly similar to those produced in vivo (Figures 2 & 3). ...
Citations
... Glutathione metabolic gene expression analysis in different cell types. T. marneffei can transit between mold and yeast forms, and this conversion process is thermally regulated 6 . Meanwhile, temperature up-shift is considered as one of the environmental stressors 24 . ...
Talaromyces marneffei is a human fungal pathogen that causes endemic opportunistic infections, especially in Southeast Asia. The key virulence factors of T. marneffei are the ability to survive host-derived heat and oxidative stress, and the ability to convert morphology from environmental mold to fission yeast forms during infection. Glutathione metabolism plays an essential role in stress response and cellular development in multiple organisms. However, the role of the glutathione system in T. marneffei is elusive. Here, we identified the genes encoding principal enzymes associated with glutathione metabolism in T. marneffei , including glutathione biosynthetic enzymes (Gcs1 and Gcs2), glutathione peroxidase (Gpx1), glutathione reductase (Glr1), and a family of glutathione S-transferase (Gst). Sequence homology search revealed an extended family of the TmGst proteins, consisting of 20 TmGsts that could be divided into several classes. Expression analysis revealed that cells in conidia, mold, and yeast phases exhibited distinct expression profiles of glutathione-related genes. Also, TmGst genes were highly upregulated in response to hydrogen peroxide and xenobiotic exposure. Altogether, our findings suggest that T. marneffei transcriptionally regulates the glutathione genes under stress conditions in a cell-type-specific manner. This study could aid in understanding the role of glutathione in thermal-induced dimorphism and stress response.
... (1) The fungus can cause an opportunistic infection called talaromycosis in immunocompromised patients, especially in people residing in an endemic area and travelers visiting Southeast Asian countries. (2)(3)(4) ...
OBJECTIVE Heat shock protein 30 (Hsp30) has been identified as an immunogenic, yeast phase-specific protein in Talaromyces marneffei. The purpose of this study was to investigate how the hsp30 gene and Hsp30 protein are expressed during phase transition and in response to heat and oxidative stress exposure. METHODS Several sequence analysis tools were employed to predict hsp30 control elements and to determine the subcellular localization of Hsp30. In the phase transition experiment, Talaromyces marneffei conidia were cultivated at two different temperatures, 25 °C and 37 °C. Subsequently, stress response tests were conducted by subjecting the yeast cells to heat at 42 °C and by treating them with hydrogen peroxide. The levels of the hsp30 transcript and its protein were measured using real-time RT-PCR and western immunoblot analysis, respectively. RESULTS The sequence analysis revealed the presence of heat response element (HRE), stress responsive element (STRE), and xenobiotic responsive element (XRE), which are typically involved in regulating hsp genes. A web-based tool predicted that Hsp30 protein is localized in cytoplasm, nucleus, and cell membrane. The hsp30 transcript and Hsp30 protein were highly clearly detected in both yeast cells and conidia. Furthermore, the hsp30 transcript in yeast cells was upregulated following heat shock at 42° C and exposure to hydrogen peroxide. These findings indicate that Hsp30 plays a crucial role in assisting the yeast phase of T. marneffei to cope with heat and oxidative stresses. CONCLUSIONS Hsp30 is a protein specific to the conidial and yeast phases of T. marneffei. It likely performs a conserved chaperone function during yeast growth and plays a significant role in stress response by mitigating protein aggregation issues. KEYWORDS Talaromyces marneffei, heat shock protein 30, expression
... Talaromyces marneffei, formerly named Penicillium marneffei is a significant emerging dimorphic fungus that can cause a severe systemic mycosis in humans across a narrow band of tropical South and Southeast Asia. [1][2][3][4][5] Recent studies have demonstrated that macrophages are the initial immune cells necessary for preventing and controlling infection with T. marneffei. [6][7][8][9][10][11] Further, previous study found that tumor necrosis factor-a (TNF-a) decreased the replication of T. marneffei in macrophages. ...
Introduction:
Recent studies have demonstrated that exosomes play roles in pathogenesis and in the treatment of various diseases. We explored the influence of exosomes released from Talaromyces marneffei (T. marneffei)-infected macrophages on human macrophages to determine whether they play a role in the pathogenesis of T. marneffei infection.
Methods:
Exosomes derived from macrophages infected with T. marneffei were extracted and characterized by transmission electron microscopy and western blot. Moreover, we examined exosomes that modulated IL-10 and TNF-α secretion and activation of p42 and p44 extracellular signal-regulated kinase 1 and 2 (ERK1/2) and activation of autophagy.
Results:
We found that exosomes promoted activation of ERK1/2 and autophagy, IL-10 and TNF-α secretion in human macrophages. Further, exosomes decreased the multiplication of T. marneffei in T. marneffei-infected human macrophages. Interestingly, exosomes isolated from T. marneffei-infected but not from uninfected macrophages can stimulate innate immune responses in resting macrophages.
Conclusion:
Our studies are the first to demonstrate that exosomes isolated from T. marneffei-infected macrophages can modulate the immune system to control inflammation, and we hypothesize that exosomes play significant roles in activation of ERK1/2 and autophagy, the replication of T. marneffei and cytokine production during T. marneffei infection.
... Talaromycosis primarily affects people with advanced HIV disease and other immunocompromised conditions, but it is becoming increasingly reported in immunocompetent individuals. Infection with T. marneffei is presumably acquired via the respiratory route and clinically presents as a disseminated illness with fever, anemia, weight loss, lymphadenopathy, hepatosplenomegaly, skin lesions and pancytopenia (Vanittanakom et al., 2006;Cooper and Vanittanakom, 2008). ...
Talaromyces (Penicillium) marneffei is an important dimorphic mycosis endemic in Southeast Asia and Southern China, but the origin and maintenance of virulence traits in this organism remains obscure. Several pathogenic fungi, including Cryptococcus neoformans, Aspergillus fumigatus, Blastomyces dermatitidis, Sporothrix schenckii, Histoplasma capsulatum and Paracoccidioides spp. interact with free living soil amoebae and data suggests that fungal pathogenic strategies may emerge from environmental interactions of these fungi with ubiquitous phagocytic microorganisms. In this study, we examined the interactions of T. marneffei with the soil amoeba Acanthamoeba castellanii. T. marneffei was rapidly ingested by A. castellanii and phagocytosis of fungal cells resulted in amoeba death after 24 h of contact. Co-culture also resulted in a rapid transition for conidia to the fission-yeast form. In addition, well-established virulence factors such as melanin and a yeast specific mannoprotein of T. marneffei were expressed during interaction with A. castellanii at 37°C. Our findings support the assumption that soil amoebae environmental predators play a role in the selection and maintenance of particular features in T. marneffei that impart virulence to this clinically important dimorphic fungus in mammalian hosts.
... the body exerts a certain protective effect against skin fungal infections becoming systemic. However, Talaromyces marneffei can grow with yeast at 37 • C, and therefore, can resist body temperature stress [50,51]. Moreover, it can tolerate the phagocytosis mechanism, surviving and replicating within the macrophage, then escaping into the cytoplasm. ...
Macrophages, the first line of defense against invasive fungi in the innate immune system, are widely distributed in the blood and tissues of the body. In response to various internal and external stimulators, macrophages can polarize into classically activated macrophages (M1) and alternatively activated macrophages (M2). These two types of polarized macrophages play different roles in antifungal activity and in maintaining the steady-state balance between inflammation and tissue repair. However, the antifungal mechanisms of M1- and M2-type macrophages have not been fully described. In this review, the immune regulatory mechanisms against pathogenic fungi of these two classical types of macrophages in various tissues are summarized. The effects of antifungal factors on macrophage differentiation are also highlighted. The description of these data, on the one hand provides valuable insight for future investigations and also highlights new strategies for the treatment of pathogenic fungal infections.
... Talaromyces marneffei, formerly named Penicillium marneffei is a signi cant emerging dimorphic fungus that can cause a severe systemic mycosis in humans across a narrow band of tropical South and Southeast Asia [1][2][3][4][5]. ...
Recent studies have shown that exosomes are involved in pathogenesis and in the treatment of various tumors and inflammatory diseases. We examined the impacts of exosomes released from Talaromyces marneffei ( T. marneffei )-infected macrophages on human macrophages to determine whether they play a role in the pathogenesis of T. marneffei infection. Exosomes derived from macrophages were extracted using commercial kits and characterized by transmission electron microscopy and western blot. Further, we examine exosomes that regulate IL-10 and TNF-α production and activation of p42 and p44 extracellular signal-regulated kinase 1 and 2 (ERK1/2) and activation of autophagy. We found that exosomes induced activation of ERK1/2 and autophagy, IL-10 and TNF-α production in human macrophages. Furthermore, exosomes decreased the replication of T. marneffei in T. marneffei -infected human macrophages. Interestingly, exosomes isolated from T. marneffei -infected but not from uninfected macrophages can stimulate a proinflammtory response in resting macrophages. Our studies are the first to demonstrate that exosomes isolated from T. marneffei -infected macrophages can induce a proinflammatory response, and we hypothesize that exosomes play significant roles in activation of ERK1/2 and autophagy, the replication of T. marneffei and cytokine release during T. marneffei infection.
... Many of these gene candidates have been identified by close examination of the characteristics of infection or by expression studies to catalog parasitic (yeast) phase-specific genes [48]. Several genes encoding phase transition and potential virulence factors have been identified to demonstrate the nature of T. marneffei virulence determinants [50][51][52][53][54]. ...
Talaromycosis (Penicilliosis) is an opportunistic mycosis caused by the thermally dimorphic fungus Talaromyces (Penicillium) marneffei. Similar to other major causes of systemic mycoses, the extent of disease and outcomes are the results of complex interactions between this opportunistic human pathogen and a host’s immune response. This review will highlight the current knowledge regarding the dynamic interaction between T. marneffei and mammalian hosts, particularly highlighting important aspects of virulence factors, intracellular lifestyle and the mechanisms of immune defense as well as the strategies of the pathogen for manipulating and evading host immune cells.
... Inhaled conidia are thought to be the infectious particles. [3][4][5] Macrophages have various cell-surface receptors that can recognize pathogen-associated molecule pattern (PAMP) of non-opsonized pathogens by the pattern recognition receptors (PRRs). 6 However, how macrophages recognize PAMP on T. marneffei is unclear. ...
Introduction
Talaromyces marneffei (T. marneffei) is an emerging pathogenic fungus. Macrophage-1 antigen (Mac-1, CR3, CD11b/CD18) is an important receptor on innate immune cells and can recognize pathogens. However, the importance of CR3 in phagocytosis of T. marneffei by macrophages and their responses to T. marneffei have not been clarified.
Methods
We show that interaction of mouse peritoneal macrophages (pMacs) or RAW264.7 macrophages with T. marneffei of its conidia spores and yeast cells enhances CR3 expression on macrophages. The phagocytosis rate was determined using flow cytometry, RT-PCR and Western blotting were used to detect CD11b expression, and the levels of IFN-γ, TNF-α, IL-2, IL-4, IL-6 and IL-10 in the co-culture supernatants were determined by ELISA.
Results
Incubation of mouse macrophages with T. marneffei promoted phagocytosis of T. marneffei, which was dramatically mitigated by pretreatment with anti-CD11b antibody or knockdown of CR3 expression on macrophages. Then, interferon γ, tumor necrosis factor α, IL-4, IL-10 and IL-12 production in macrophages incubation with heat-killed T. marneffei was detected. CD11b expression on mouse macrophages was upregulated by T. marneffei. Incubation of T. marneffei promoted phagocytosis of T. marneffei by macrophages and high levels of pro-inflammatory and anti-inflammatory cytokine production by macrophages, which were mitigated and abrogated by pre-treatment with anti-CD11b or knockdown of CD11b expression.
Conclusion
These data indicated that murine macrophage requires CD11b to recognize Talaromyces marneffei and their cytokine responses to heat-killed T. marneffei in vitro.
... Human penicilliosis is believed to be initiated by inhalation of conidia which are subsequently phagocytosed by alveolar macrophages. They survive in the Clinically, only the yeast form is found in tissues and peripheral blood (3,39). Only a few studies on cell mediated immune response toward T. marneffei were available in the literature. ...
Talaromyces (Penicillium) marneffei is an AIDS-defining infection in Southeast Asia and is associated with high mortality. It is rare in non-immunosuppressed individuals, especially children. Little is known about host immune response and genetic susceptibility to this endemic fungus. Genetic defects in the interferon-gamma (IFN-γ)/STAT1 signaling pathway, CD40/CD40 ligand- and IL12/IL12-receptor-mediated crosstalk between phagocytes and T-cells, and STAT3-mediated Th17 differentiation have been reported in HIV-negative children with talaromycosis and other endemic mycoses such as histoplasmosis, coccidioidomycosis, and paracoccidioidomycosis. There is a need to design a diagnostic algorithm to evaluate such patients. In this article, we review a cohort of pediatric patients with disseminated talaromycosis referred to the Asian Primary Immunodeficiency Network for genetic diagnosis of PID. Using these illustrative cases, we propose a diagnostics pipeline that begins with immunoglobulin pattern (IgG, IgA, IgM, and IgE) and enumeration of lymphocyte subpopulations (T-, B-, and NK-cells). The former could provide clues for hyper-IgM syndrome and hyper-IgE syndrome. Flow cytometric evaluation of CD40L expression should be performed for patients suspected to have X-linked hyper-IgM syndrome. Defects in interferon-mediated JAK-STAT signaling are evaluated by STAT1 phosphorylation studies by flow cytometry. STAT1 hyperphosphorylation in response to IFN-α or IFN-γ and delayed dephosphorylation is diagnostic for gain-of-function STAT1 disorder, while absent STAT1 phosphorylation in response to IFN-γ but normal response to IFN-α is suggestive of IFN-γ receptor deficiency. This simple and rapid diagnostic algorithm will be useful in guiding genetic studies for patients with disseminated talaromycosis requiring immunological investigations.
... Pada 25 o C-30 o C, jamur berbentuk kapang, sedangkan pada suhu 37 o C membentuk ragi. 1,18,19 Sifat tersebut menyebabkan T. marneffei mampu menginfeksi manusia. ...
... Talaromyces marneffei membentuk konidiofora dan konidia (spora) di alam. 1 Konidia mudah menyebar dan masuk ke dalam tubuh manusia melalui inhalasi. 18 Beberapa penelitian menunjukkan bahwa jamur ini paling banyak diisolasi dari paru, 21-23 diikuti hati dan limpa. 22,23 Hal tersebut mendukung teori bahwa patogenesis T. marneffei yang diawali inhalasi konidia dari alam kemudian menyebar ke organ lain secara hematogen. ...
... Talaromyces marneffei memiliki kemampuan bertahan dalam lingkungan tidak menguntungkan di dalam sel fagosit bahkan mampu melakukan proliferasi dengan cara membelah diri di dalam sel fagosit. 18 Derajat keparahan infeksi bervariasi tergantung pada derajat imunokompromi. Pasien dengan HIV umumnya memiliki infeksi diseminata yang meliputi berbagai organ. ...
Talaromycosis marneffei is a mycotic disease caused by Talaromyces marneffei which primarily infectimmunocompromised patient. This disease is endemic in Southeast Asia, and Indonesia consider as endemic area dueto a case of tourist who got the infection after visiting Indonesia. Diagnosis was made based on clinical suspicion withlaboratory confirmation. Clinical manifestations are not specific, such as fever, anemia, weight loss, lymphadenopathy,hepatomegaly, splenomegaly, respiratory disorder, and cutaneous manifestation. Histopathology and culture are themost common examination performed for diagnosis. In histopathology examination, fungi appear as fission arthroconidiacells which shape round to oval, with cross wall formation inside or outside macrophage and histiocyte. Thermaldimorphism characteristic can be observed in fungal culture. Fungi grows as mold at 25oC-30oC and as yeast at 37oC.Definitive identification of T. marneffei was done by molecular examination using primers derived from ITS region asprimary marker and beta tubulin region as secondary marker. Talaromyces marneffei is sapronosis, that transmitted viainhalation of conidia from environment.
