Lipid Secretion by Parasitic Cells of Coccidioides Contributes to Disseminated Disease.
Lipid Secretion by Parasitic Cells of Coccidioides Contributes to Disseminated Disease.
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DOI：
10.3389/fcimb.2021.592826
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发表时间：
2021
影响因子：
5.7
通讯作者：
Cole GT
中科院分区：
文献类型：
--
作者：
Peláez-Jaramillo CA;Jiménez-Alzate MDP;Araque-Marin P;Hung CY;Castro-Lopez N;Cole GT
球孢子菌是一种土传真菌病原体，也是美国西南部、墨西哥、中美洲和南美洲半沙漠地区流行的人类呼吸道疾病（球孢子菌病）的病原体。哺乳动物宿主吸入的雾化节分孢子首先转化为大寄生细胞（小球，直径 80-100 μm），然后发生内孢子形成，这是小球内容物产生多个内生孢子的过程。后者在母体小球破裂时释放并建立新的肺部感染灶。内孢子形成之前小球成熟的一个新特征是在寄生细胞生长期间体内脱落的富含脂质的膜细胞表面层的分泌，以及在体外生长期间分泌到液体培养基中。对培养物来源的小球外壁 (SOW) 部分的化学分析表明，它主要由磷脂组成，并富含饱和脂肪酸，包括肉豆蔻酸、棕榈酸、反油酸、油酸和硬脂酸。 NMR揭示了单糖和二糖连接的酰基甘油和鞘脂的存在。主要鞘脂成分是鞘氨醇和神经酰胺。来自与 SOW 脂质一起孵育的健康 C57BL/6 和 DBA/2 小鼠的原代中性粒细胞显示，与仅与节分孢子一起孵育的中性粒细胞相比，对活的节分孢子球孢子菌的杀菌活性显着降低。宿主细胞暴露于 SOW 脂质对中性粒细胞活力没有影响。此外，在存在分离的SOW组分的情况下，用节孢子球孢子皮下攻击的C57BL/6小鼠出现了播散性疾病，而通过相同途径仅用节孢子虫攻击的对照小鼠没有表现出感染播散。我们假设 SOW 脂质有助于抑制球孢子菌感染的炎症反应。目前正在进行研究来表征 SOW 脂质的免疫抑制机制。
Coccidioides is a soil-borne fungal pathogen and causative agent of a human respiratory disease (coccidioidomycosis) endemic to semi-desert regions of southwestern United States, Mexico, Central and South America. Aerosolized arthroconidia inhaled by the mammalian host first undergo conversion to large parasitic cells (spherules, 80–100 μm diameter) followed by endosporulation, a process by which the contents of spherules give rise to multiple endospores. The latter are released upon rupture of the maternal spherules and establish new foci of lung infection. A novel feature of spherule maturation prior to endosporulation is the secretion of a lipid-rich, membranous cell surface layer shed in vivo during growth of the parasitic cells and secretion into liquid culture medium during in vitro growth. Chemical analysis of the culture derived spherule outer wall (SOW) fraction showed that it is composed largely of phospholipids and is enriched with saturated fatty acids, including myristic, palmitic, elaidic, oleic, and stearic acid. NMR revealed the presence of monosaccharide- and disaccharide-linked acylglycerols and sphingolipids. The major sphingolipid components are sphingosine and ceramide. Primary neutrophils derived from healthy C57BL/6 and DBA/2 mice incubated with SOW lipids revealed a significant reduction in fungicidal activity against viable Coccidioides arthroconidia compared to incubation of neutrophils with arthroconidia alone. Host cell exposure to SOW lipids had no effect on neutrophil viability. Furthermore, C57BL/6 mice that were challenged subcutaneously with Coccidioides arthroconidia in the presence of the isolated SOW fraction developed disseminated disease, while control mice challenged with arthroconidia alone by the same route showed no dissemination of infection. We hypothesize that SOW lipids contribute to suppression of inflammatory response to Coccidioides infection. Studies are underway to characterize the immunosuppressive mechanism(s) of SOW lipids.
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影响因子：
--
作者：
Bertini, Silvio;Colombo, Arnaldo L.;Straus, Anita H.
通讯作者：
Straus, Anita H.
影响因子：
6.5
作者：
Ichihara, Ken'ichi;Fukubayashi, Yumeto
通讯作者：
Fukubayashi, Yumeto
影响因子：
3.1
作者：
Hung, CY;Ampel, NM;Cole, GT
通讯作者：
Cole, GT
影响因子：
3.1
作者：
Hung, Chiung-Yu;Jimenez-Alzate, Maria del Pilar;Cole, Garry T.
通讯作者：
Cole, Garry T.
DOI：
10.4049/jimmunol.1201719
发表时间：
2012-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kaplan MJ;Radic M
通讯作者：
Radic M