Tsitsigiannis Dimitrios I, Bok Jin-Woo, Andes David, Nielsen Kristian Fog, Frisvad Jens C, Keller Nancy P
Department of Plant Pathology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Infect Immun. 2005 Aug;73(8):4548-59. doi: 10.1128/IAI.73.8.4548-4559.2005.
Oxylipins comprise a family of oxygenated fatty acid-derived signaling molecules that initiate critical biological activities in animals, plants, and fungi. Mammalian oxylipins, including the prostaglandins (PGs), mediate many immune and inflammation responses in animals. PG production by pathogenic microbes is theorized to play a role in pathogenesis. We have genetically characterized three Aspergillus genes, ppoA, ppoB, and ppoC, encoding fatty acid oxygenases similar in sequence to specific mammalian prostaglandin synthases, the cyclooxygenases. Enzyme-linked immunosorbent assay analysis showed that production of PG species is decreased in both Aspergillus nidulans and A. fumigatus ppo mutants, implicating Ppo activity in generating PGs. The A. fumigatus triple-ppo-silenced mutant was hypervirulent in the invasive pulmonary aspergillosis murine model system and showed increased tolerance to H(2)O(2) stress relative to that of the wild type. We propose that Ppo products, PG, and/or other oxylipins may serve as activators of mammalian immune responses contributing to enhanced resistance to opportunistic fungi and as factors that modulate fungal development contributing to resistance to host defenses.
氧化脂质是一类由氧化脂肪酸衍生而来的信号分子家族，它们在动物、植物和真菌中引发关键的生物活性。哺乳动物的氧化脂质，包括前列腺素（PGs），介导动物体内的许多免疫和炎症反应。据推测，致病微生物产生的PG在发病机制中起作用。我们已经对三个曲霉基因ppoA、ppoB和ppoC进行了基因特征分析，它们编码的脂肪酸加氧酶在序列上与特定的哺乳动物前列腺素合酶即环氧化酶相似。酶联免疫吸附测定分析表明，在构巢曲霉和烟曲霉的ppo突变体中，PG种类的产生均减少，这表明Ppo活性与PG的生成有关。在侵袭性肺曲霉病小鼠模型系统中，烟曲霉三ppo沉默突变体具有高毒力，并且相对于野生型，其对H₂O₂胁迫的耐受性增强。我们提出，Ppo产物、PG和/或其他氧化脂质可能作为哺乳动物免疫反应的激活剂，有助于增强对机会性真菌的抵抗力，并且作为调节真菌发育的因子，有助于抵抗宿主防御。
