Univ Angers, Univ Brest, IRF, SFR ICAT, 49000 Angers, France.
Laboratory of Bioinformatics, Biomathematics and Biostatistics-LR16IPT09, Institut Pasteur de Tunis, Tunis, Tunisia.
Cytokine. 2023 Dec;172:156384. doi: 10.1016/j.cyto.2023.156384. Epub 2023 Oct 11.
Fungal infections caused by Scedosporium species are rising among immunocompromised and immunocompetent patients. Within the immunocompetent group, patients with cystic fibrosis (pwCF) are at high risk of developing a chronic airway colonization by these molds. While S. apiospermum is one of the major species encountered in the lungs of pwCF, S. dehoogii has rarely been reported. The innate immune response is believed to be critical for host defense against fungal infections. However, its role has only recently been elucidated and the immune mechanisms against Scedosporium species are currently unknown. In this context, we undertook a comparative investigation of macrophage-mediated immune responses toward S. apiospermum and S. dehoogii conidia. Our data showed that S. apiospermum and S. dehoogii conidia strongly stimulated the expression of a set of pro-inflammatory cytokines and chemokines such as IL-1β, IL-8, IL-6 and TNFα. We demonstrated that S. dehoogii was more potent in stimulating the early release of pro-inflammatory cytokines and chemokines while S. apiospermum induced a late inflammatory response at a higher level. Flow cytometry analysis showed that M1-like macrophages were able to internalize both S. apiospermum and S. dehoogii conidia, with a similar intracellular killing rate for both species. In conclusion, these results suggest that M1-like macrophages can rapidly initiate a strong immune response against both S. apiospermum and S. dehoogii. This response is characterized by a similar killing of internalized conidia, but a different time course of cytokine production.
棘孢木霉属真菌引起的真菌感染在免疫功能低下和免疫功能正常的患者中呈上升趋势。在免疫功能正常的人群中，囊性纤维化（pwCF）患者极易被这些霉菌慢性气道定植。虽然 S. apiospermum 是在 pwCF 肺部发现的主要菌种之一，但 S. dehoogii 很少被报道。先天免疫反应被认为对宿主抵御真菌感染至关重要。然而，其作用直到最近才被阐明，目前尚不清楚针对棘孢木霉属物种的免疫机制。在这种情况下，我们对巨噬细胞介导的针对 S. apiospermum 和 S. dehoogii 分生孢子的免疫反应进行了比较研究。我们的数据表明，S. apiospermum 和 S. dehoogii 分生孢子强烈刺激了一组促炎细胞因子和趋化因子的表达，如 IL-1β、IL-8、IL-6 和 TNFα。我们证明 S. dehoogii 更能刺激早期促炎细胞因子和趋化因子的释放，而 S. apiospermum 以更高的水平诱导晚期炎症反应。流式细胞术分析表明，M1 样巨噬细胞能够内化 S. apiospermum 和 S. dehoogii 分生孢子，两种物种的细胞内杀伤率相似。总之，这些结果表明 M1 样巨噬细胞可以迅速对 S. apiospermum 和 S. dehoogii 发起强烈的免疫反应。这种反应的特点是内化的分生孢子具有相似的杀伤能力，但细胞因子产生的时间过程不同。
