LC3-associated phagocytosis in macrophage responses to Paracoccidioides spp.

IF 1.9 4区医学 Q2 PARASITOLOGY

Memorias do Instituto Oswaldo Cruz Pub Date : 2026-03-06 DOI:10.1590/0074-02760250089

Getúlio Pereira de Oliveira Júnior, Herdson Renney de Sousa, Kaio César de Melo Gorgonha, Lara Laís Montalvão Tomaz, Tatiana Karla Dos Santos Borges, Kellyanne Teixeira Rangel, Scott Fabricant, Fernanda Koser Gustafson, Lucas Friaça Albuquerque, Angelo Rossi Neto, Fabián Andrés Hurtado, Hugo Costa Paes, Arturo Casadevall, Ildinete Silva-Pereira, Maria Sueli Soares Felipe, Patrícia Albuquerque, André Moraes Nicola

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引用次数: 0

Abstract

Background: Paracoccidioidomycosis (PCM) is a systemic infection that is endemic to Latin America, caused by thermodimorphic fungi from the Paracoccidioides genus. These fungi are facultative intracellular parasites of macrophages. LC3-associated phagocytosis (LAP), a non-canonical form of autophagy, plays a critical role in the response of these phagocytes to similar pathogens.

Objectives: In this study, we investigated the role of LAP in the macrophage responses to Paracoccidioides spp.

Methods: We detected LAP in macrophages infected with Paracoccidioides spp by immunofluorescence microscopy with antibodies to LC3. Piceatannol and diphenyleneiodonium chloride (DPI), respectively Syk and nicotinamide adenine dinucleotide phosphate oxidase (NADPH) inhibitors, were used to understand the role their pathways played. To determine the function of LAP, we targeted ATG5, a key autophagy gene, by RNA interference.

Findings: We observed LC3 recruitment to phagosomes containing Paracoccidioides spp. in RAW264.7 and J774.16 cell lines and in bone marrow-derived macrophages. ATG5 RNA interference reduced the antifungal activity of J774.16 cells, highlighting the importance of LC3 recruitment for effective fungal control. Interestingly, pharmacological inhibition of Syk kinase and NADPH oxidase pathways, essential for LAP against Aspergillus fumigatus and Candida albicans, did not impair LAP against P. brasiliensis.

Main conclusions: This suggests distinct triggering mechanisms, possibly due to differences in the fungal cell surface composition. These findings suggest that LAP plays a significant role in the host defense against Paracoccidioides spp. and may represent a promising target for host-directed PCM therapies.

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巨噬细胞对副球虫反应中的lc3相关吞噬作用。第一轮综述-评论者评论

背景：副球孢子菌病（PCM）是拉丁美洲特有的一种全身性感染，由副球孢子菌属的热致真菌引起。这些真菌是巨噬细胞的兼性细胞内寄生虫。lc3相关吞噬（LAP）是一种非典型的自噬形式，在这些吞噬细胞对类似病原体的反应中起着关键作用。目的：研究LAP在巨噬细胞对副球孢子虫的免疫应答中的作用。方法：应用免疫荧光显微镜检测巨噬细胞感染副球孢子虫后的LAP。利用皮杉醇和二苯二氯铵（DPI）分别作为Syk和烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NADPH）抑制剂，了解它们的途径所起的作用。为了确定LAP的功能，我们通过RNA干扰靶向自噬关键基因ATG5。结果：我们在RAW264.7和J774.16细胞系以及骨髓源性巨噬细胞中观察到LC3向含有副球蚴的吞噬体募集。ATG5 RNA干扰降低了J774.16细胞的抗真菌活性，突出了LC3募集对有效控制真菌的重要性。有趣的是，药理学抑制Syk激酶和NADPH氧化酶途径对LAP对抗烟曲霉和白色念珠菌至关重要，但并不影响LAP对抗巴西疟原虫。主要结论：这表明不同的触发机制，可能是由于真菌细胞表面组成的差异。这些发现表明，LAP在宿主对副球虫的防御中起着重要作用，可能是宿主定向PCM治疗的一个有希望的靶点。

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来源期刊

Memorias do Instituto Oswaldo Cruz 医学-寄生虫学

CiteScore

5.00

自引率

3.60%

发文量

审稿时长

3-8 weeks

期刊介绍： Memórias do Instituto Oswaldo Cruz is a journal specialized in microbes & their vectors causing human infections. This means that we accept manuscripts covering multidisciplinary approaches and findings in the basic aspects of infectious diseases, e.g. basic in research in prokariotes, eukaryotes, and/or virus. Articles must clearly show what is the main question to be answered, the hypothesis raised, and the contribution given by the study. Priority is given to manuscripts reporting novel mechanisms and general findings concerning the biology of human infectious prokariotes, eukariotes or virus. Papers reporting innovative methods for diagnostics or that advance the basic research with these infectious agents are also welcome. It is important to mention what we do not publish: veterinary infectious agents research, taxonomic analysis and re-description of species, epidemiological studies or surveys or case reports and data re-analysis. Manuscripts that fall in these cases or that are considered of low priority by the journal editorial board, will be returned to the author(s) for submission to another journal.