Histoplasma is an endemic dimorphic fungus that can cause disease in healthy and immunocompromised individuals after the transition of inhaled spores into the facultative intracellular yeast form. There is substantial diversity among Histoplasma species, but it is not clear how this heterogeneity impacts the progression of pathology and cellular immune responses during acute respiratory infection, which represents the vast majority of histoplasmosis disease burden. After inoculating mice intranasally with a sublethal inoculum, we characterized the immune response to Histoplasma capsulatum (strain G186A) and Histoplasma ohiense (strain G217B) using comprehensive flow cytometric and single-cell analyses. Within 8 days after inoculation, H. ohiense induced a significantly higher infiltration of neutrophils and inflammatory monocytes into the lung compared to H. capsulatum. Microscopic analysis of infected lung tissue revealed that although the total number of fungi was similar within inflamed lung lesions, we observed different species-dependent intracellular yeast distribution patterns. Inoculation with gfp-expressing strains indicated that H. ohiense, but not H. capsulatum, was associated primarily with alveolar macrophages early after infection. Interestingly, we observed a significant reduction in the total number of alveolar macrophages 12 to 16 days after H. ohiense, but not H. capsulatum infection, despite similar intracellular growth dynamics within AMJ2-C11 alveolar macrophages in vitro. Together, our data suggest that H. ohiense, but not H. capsulatum, preferentially interacts with alveolar macrophages early after infection, which may lead to a different course of inflammation and resolution despite similar rates of fungal clearance.

中文翻译：

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生物多样性的组织胞浆菌物种在亚致死感染后引发不同的肺部炎症模式。

组织胞浆菌是一种地方性双相真菌，可在吸入的孢子转变为兼性细胞内酵母形式后，在健康和免疫功能低下的个体中引起疾病​​。组织胞浆菌属物种之间存在很大的多样性，但尚不清楚这种异质性如何影响急性呼吸道感染期间的病理学和细胞免疫反应的进展，急性呼吸道感染代表了绝大多数的组织胞浆菌病疾病负担。在用亚致死接种物鼻内接种小鼠后，我们使用综合流式细胞术和单细胞分析表征了对荚膜组织胞浆菌（G186A 株）和Histoplasma ohiense（G217B株）的免疫反应。接种后8天内，与H. capsulatum相比，H . ohiense诱导显着更高的嗜中性粒细胞和炎性单核细胞浸润到肺中。受感染肺组织的显微分析显示，虽然发炎的肺病灶内真菌的总数相似，但我们观察到不同的物种依赖性细胞内酵母分布模式。用表达gfp的菌株接种表明H. ohiense而不是H. capsulatum主要与感染后早期的肺泡巨噬细胞相关。有趣的是，我们观察到在H. ohiense后 12 到 16 天肺泡巨噬细胞总数显着减少，但没有H. capsulatum感染，尽管体外AMJ2-C11 肺泡巨噬细胞内的细胞内生长动力学相似。总之，我们的数据表明H. ohiense而不是H. capsulatum，在感染后早期优先与肺泡巨噬细胞相互作用，尽管真菌清除率相似，但这可能导致不同的炎症过程和消退。