Neutrophil Cells Are Essential for The Efficacy of a Therapeutic Vaccine against Paracoccidioidomycosis.
Neutrophil Cells Are Essential for The Efficacy of a Therapeutic Vaccine against Paracoccidioidomycosis.
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DOI：
10.3390/jof7060416
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发表时间：
2021-05-26
期刊：
影响因子：
--
通讯作者：
Taborda CP
中科院分区：
文献类型：
--
作者：
Dias LDS;Silva LBR;Nosanchuk JD;Taborda CP
副球孢子菌病（PCM），由副球孢子菌属物种引起，是一种系统性疾病，在几个拉丁美洲国家，主要是在巴西，哥伦比亚，阿根廷和委内瑞拉。目前的治疗方法是具有挑战性的，因为它们需要长时间的抗真菌药物，具有潜在的毒性，尽管抗真菌药物，复发是常见的。因此，正在研究新的治疗方法，如疫苗。由与脂质阳离子DODAB缔合的肽P10（P10+DODAB）组成的治疗性疫苗在PCM的鼠模型中是有效的。然而，保护性反应所需的特定免疫机制尚未完全阐明。本工作旨在评估中性粒细胞参与P10+DODAB诱导的免疫应答。我们发现，与未接受这种治疗的感染动物相比，疫苗减少了肺中性粒细胞的流入和真菌负荷。P10+ DODAB处理的动物的肺实质结构在很大程度上保留，仅存在少量肉芽肿，组织细胞因子分析显示Th 1细胞因子谱，IL-12、IFN-γ和TNF-α水平增加，IL-4水平低。当中性粒细胞在每次治疗前24小时耗尽时，P10+DODAB疫苗的有效性完全丧失，因为真菌负荷仍然很高，组织学检查显示明显的炎症和真菌传播，伴有失调的细胞因子应答。总之，这些发现表明中性粒细胞对于确保触发对P10+DODAB的有效免疫应答至关重要。
Paracoccidioidomycosis (PCM), caused by the Paracoccidioides species, is a systemic disease endemic in several Latin American countries, mainly in Brazil, Colombia, Argentina, and Venezuela. Current treatment approaches are challenging as they require prolonged durations of antifungal drugs that have potential toxicities, and despite antifungals, relapses are common. Hence, new therapeutic approaches, such as vaccines, are being investigated. The therapeutic vaccine consisting of peptide P10 associated with lipid cationic DODAB (P10+DODAB) is effective in murine models of PCM. However, the specific immune mechanisms required for the protective response has not been fully elucidated. The present work aims at evaluating the participation of neutrophils in the immune response induced by P10+DODAB. We found that the vaccine reduced both the influx of pulmonary neutrophils and the fungal load in comparison to infected animals that did not receive this treatment. The parenchymal architecture of the lungs of P10+DODAB-treated animals was largely preserved with only a few granulomas present, and tissue cytokine analysis showed a Th1 cytokine profile with augmented levels of IL-12, IFN-γ and TNF-α, and low levels of IL-4. When neutrophils were depleted 24 h prior to each treatment, the effectiveness of the P10+DODAB vaccine was completely lost as the fungal burdens remained high and histological examination showed a marked inflammation and fungal dissemination with a dysregulated cytokine response. In conclusion, these findings indicate that neutrophils are vital to ensure the triggering of an effective immune response to P10+DODAB.
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影响因子：
3.8
作者：
de Oliveira LL;Coltri KC;Cardoso CR;Roque-Barreira MC;Panunto-Castelo A
通讯作者：
Panunto-Castelo A
中性粒细胞在免疫，炎症及以后的各种新型功能。
DOI：
10.1084/jem.20122220
发表时间：
2013-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mócsai A
通讯作者：
Mócsai A
影响因子：
9
作者：
Marwick JA;Mills R;Kay O;Michail K;Stephen J;Rossi AG;Dransfield I;Hirani N
通讯作者：
Hirani N
影响因子：
16.6
作者：
Hampton, Henry R.;Bailey, Jacqueline;Tomura, Michio;Brink, Robert;Chtanova, Tatyana
通讯作者：
Chtanova, Tatyana
影响因子：
2.9
作者：
Hrycyk, Marluce Francisca;Garces, Hans Garcia;Bagagli, Eduardo
通讯作者：
Bagagli, Eduardo