Abstract
Talaromycosis (penicilliosis) caused by Talaromyces marneffei is one of the most important opportunistic infection diseases in tropical countries of South and Southeast Asia. Most infections occurred in individuals with human immunodeficiency virus (HIV) and the primarily reason for the increase in the number of the cases is HIV pandemic. The pathogenesis of T. marneffei infection is unclear. There is still no ideal animal model for studying talaromycosis. In this study, we developed a stable, safe and maneuverable murine model that mimics human T. marneffei disseminated infection using T. marneffei yeast intraperitoneal injected to BALB/c nude mice. We successfully observed symptoms similar to those seen in clinical patients in this murine model, including skin lesions, hepatosplenomegaly, pulmonary infection and mesenteric lesions. We further studied the pathological changes of various tissues and organs in the infected animals to help better understand the severity of the infection. This model may provide a good tool for studying disseminated infection induced by T. marneffei.
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References
Samson RA, Yilmaz N, Houbraken J, et al. Phylogeny and nomenclature of the genus Talaromyces and taxa accommodated in Penicillium subgenus Biverticillium. Stud Mycol. 2011;70:159–83. https://doi.org/10.3114/sim.2011.70.04.
Vanittanakom N, Cooper CR Jr, Fisher MC, et al. Penicillium marneffei infection and recent advances in the epidemiology and molecular biology aspects. Clin Microbiol Rev. 2006;19:95–110. https://doi.org/10.1128/cmr.19.1.95-110.2006.
Limper AH, Adenis A, Le T, et al. Fungal infections in HIV/AIDS. Lancet Infect Dis. 2017;17:e334-43. https://doi.org/10.1016/s1473-3099(17)30303-1.
Nittayananta W. Penicilliosis marneffei: another AIDS defining illness in Southeast Asia. Oral Dis. 1999;5:286–93. https://doi.org/10.1111/j.1601-0825.1999.tb00091.x.
Jiang J, Meng S, Huang S, et al. Effects of Talaromyces marneffei infection on mortality of HIV/AIDS patients in southern China: a retrospective cohort study. Clin Microbiol Infect: Off Publ Eur Soc Clin Microbiol Infect Dis. 2019;25:233–41. https://doi.org/10.1016/j.cmi.2018.04.018.
Hu Y, Zhang J, Li X, et al. Penicillium marneffei infection: an emerging disease in mainland China. Mycopathologia. 2013;175:57–67. https://doi.org/10.1007/s11046-012-9577-0.
Chariyalertsak S, Supparatpinyo K, Sirisanthana T, et al. A controlled trial of itraconazole as primary prophylaxis for systemic fungal infections in patients with advanced human immunodeficiency virus infection in Thailand. Clin Infect Dis: Off Publ Infect Dis Soc Am. 2002;34:277–84. https://doi.org/10.1086/338154.
Son VT, Khue PM, Strobel M. Penicilliosis and AIDS in Haiphong, Vietnam: evolution and predictive factors of death. Med et Maladies Infect. 2014;44:495–501. https://doi.org/10.1016/j.medmal.2014.09.008.
Waterston RH, Lindblad-Toh K, Birney E, et al. Initial sequencing and comparative analysis of the mouse genome. Nature. 2002;420:520–62. https://doi.org/10.1038/nature01262.
Sun J, Li X, Feng P, et al. RNAi-mediated silencing of fungal acuD gene attenuates the virulence of Penicillium marneffei. Med Mycol. 2014;52:167–78. https://doi.org/10.1093/mmy/myt006.
Kudeken N, Kawakami K, Kusano N, et al. Cell-mediated immunity in host resistance against infection caused by Penicillium marneffei. J Med Vet Mycol: Bi-monthly Pub Int Soc Human and Animal Mycol. 1996;34:371–8. https://doi.org/10.1080/02681219680000671.
Liu Y, Huang X, Yi X, et al. Detection of talaromyces marneffei from fresh tissue of an inhalational murine pulmonary model using nested PCR. PLoS ONE. 2016;11:e0149634. https://doi.org/10.1371/journal.pone.0149634.
Duong TA. Infection due to Penicillium marneffei, an emerging pathogen: review of 155 reported cases. Clin Infect Dis: An Off Pub Infect Dis Soc Am. 1996;23:125–30. https://doi.org/10.1093/clinids/23.1.125.
Cao C, Xi L, Chaturvedi V. Talaromycosis (Penicilliosis) due to Talaromyces (Penicillium) marneffei: insights into the clinical trends of a major fungal disease 60 years after the discovery of the pathogen. Mycopathologia. 2019;184:709–20. https://doi.org/10.1007/s11046-019-00410-2.
Chan YF, Chow TC. Ultrastructural observations on Penicillium marneffei in natural human infection. Ultrastruct Pathol. 1990;14:439–52. https://doi.org/10.3109/01913129009007223.
Huang X, Li D, Xi L, et al. Galleria mellonella larvae as an infection model for penicillium marneffei. Mycopathologia. 2015;180:159–64. https://doi.org/10.1007/s11046-015-9897-y.
Borman AM, Fraser M, Szekely A, et al. Rapid and robust identification of clinical isolates of Talaromyces marneffei based on MALDI-TOF mass spectrometry or dimorphism in Galleria mellonella. Med Mycol. 2019;57:969–75. https://doi.org/10.1093/mmy/myy162.
Huang X, Li D, Xi L, et al. Caenorhabditis elegans: a simple nematode infection model for Penicillium marneffei. PLoS ONE. 2014;9:e108764. https://doi.org/10.1371/journal.pone.0108764.
Feng J, Chen Z, He L, et al. AcuD Gene Knockout Attenuates the Virulence of Talaromyces marneffei in a Zebrafish Model. Mycobiology. 2019;47:207–16. https://doi.org/10.1080/12298093.2019.1620975.
Pazhakh V, Ellett F, Croker BA. β-glucan-dependent shuttling of conidia from neutrophils to macrophages occurs during fungal infection establishment. PLoS Biol. 2019;17:e3000113. https://doi.org/10.1371/journal.pbio.3000113.
Ellett F, Pazhakh V, Pase L, et al. Macrophages protect Talaromyces marneffei conidia from myeloperoxidase-dependent neutrophil fungicidal activity during infection establishment in vivo. 2018;14:e1007063. https://doi.org/10.1371/journal.ppat.1007063.
Funding
This research was funded by grants from Project for AIDS Bureau of Yunnan Province; “Ten-thousand Talents Program" of Yunnan Province (YNWR-MY-2018–039); Natural Science Foundation of China (81560325, 81660737); Yunnan Province Clinical Research Center for Skin Immune Diseases(2019ZF012);Yunnan Province Clinical Center for Skin Immune Diseases (ZX2019-03–02);Innovation Team of Department of Science and Technology of Yunnan Province (2018HC005).
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Conceived and designed the experiments: RW YL. Performed the experiments: JH JL HX JL ZL HZ. Analyzed the data: JH YK HL. Contributed reagents/materials/analysis tools: HL RW YL. Contributed to the writing of themanuscript: JH RW YL.
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He, J., Li, JS., Xu, HY. et al. A Reliable Murine Model of Disseminated Infection Induced by Talaromyces Marneffei. Mycopathologia 187, 53–64 (2022). https://doi.org/10.1007/s11046-021-00596-4
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DOI: https://doi.org/10.1007/s11046-021-00596-4