T helper 1-inducing adjuvant protects against experimental paracoccidioidomycosis.
T helper 1-inducing adjuvant protects against experimental paracoccidioidomycosis.
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DOI：
10.1371/journal.pntd.0000183
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发表时间：
2008-03-12
影响因子：
3.8
通讯作者：
Panunto-Castelo A
中科院分区：
文献类型：
--
作者：
de Oliveira LL;Coltri KC;Cardoso CR;Roque-Barreira MC;Panunto-Castelo A
免疫刺激疗法是一种很有前途的方法来改善治疗全身性真菌感染，如副球孢子菌病（PCM），其药物治疗通常是长期的，并伴有毒副作用和复发。目前的研究是为了确定在巴西疟原虫感染的小鼠中注射T辅助（Th） 1刺激佐剂是否对实验性PCM的过程有有益的影响。为此，在感染后第20天，小鼠被感染并接受完全弗氏佐剂（CFA），一种成熟的Th1实验诱导剂或不完全弗氏佐剂（IFA -对照组）治疗。治疗4周后，服用cfa的小鼠肺部出现轻度感染，其特征是没有上皮样细胞肉芽肿和酵母细胞，而对照组小鼠出现多处局灶性上皮样肉芽肿，伴有淋巴细胞晕，周围有大量活的和不活的酵母细胞。此外，与对照组相比，CFA给药诱导真菌负荷减少2.4 log (bbb99 %)，并导致免疫反应的改善，逆转了对照组观察到的免疫抑制。th1诱导佐剂的免疫治疗已被批准用于人类，可能是治疗PCM的一种有价值的工具，对提高人类临床治愈率有潜在的作用。巴西疟原虫是一种热二态的人类致病真菌，可引起副球孢子菌病（PCM）， PCM是拉丁美洲最普遍的人类系统性真菌病，其药物治疗通常需要很长时间，并伴有毒副作用和复发。虽然免疫刺激疗法是一种很有希望改善真菌感染治疗的方法，但很少有研究报道。在目前的研究中，我们验证了在巴西螺孢子虫感染小鼠中单剂量给药诱导辅助性T (Th) 1免疫应答（完全弗氏佐剂[CFA]）足以打破感染小鼠对真菌缺乏免疫应答的现象。治疗4周后，服用cfa的小鼠肺部出现轻度感染，肺部结构保存完好，真菌负荷较小，而服用不完全弗氏佐剂的对照组小鼠出现许多肉芽肿病变和高真菌负荷。th1诱导佐剂的免疫治疗可能是治疗PCM的一种有价值的工具，对人类PCM的快速有效治疗具有潜在的价值。
Immunostimulatory therapy is a promising approach to improving the treatment of systemic fungal infections such as paracoccidioidomycosis (PCM), whose drug therapy is usually prolonged and associated with toxic side effects and relapses. The current study was undertaken to determine if the injection of a T helper (Th) 1–stimulating adjuvant in P. brasiliensis–infected mice could have a beneficial effect on the course of experimental PCM. For this purpose, mice were infected and treated with complete Freund's adjuvant (CFA), a well-established Th1 experimental inductor, or incomplete Freund's adjuvant (IFA - control group) on day 20 postinfection. Four weeks after treatment, the CFA-treated mice presented a mild infection in the lungs characterized by absence of epithelioid cell granulomas and yeast cells, whereas the control mice presented multiple sites of focal epithelioid granulomas with lymphomonocytic halos circumscribing a high number of viable and nonviable yeast cells. In addition, CFA administration induced a 2.4 log reduction (>99%) in the fungal burden when compared to the control group, and led to an improvement of immune response, reversing the immunosuppression observed in the control group. The immunotherapy with Th1-inducing adjuvant, approved to be used in humans, might be a valuable tool in the treatment of PCM and potentially useful to improve the clinical cure rate in humans. P. brasiliensis is a thermally dimorphic human pathogenic fungus that causes paracoccidioidomycosis (PCM), the most prevalent human systemic mycosis in Latin America, whose drug therapy is usually prolonged and associated with toxic side effects and relapses. Although immunostimulatory therapy is a promising approach to improving the treatment of fungal infections as PCM, few studies have been reported. In the current study, we verified that a single-dose administration of an adjuvant that induces T helper (Th) 1 immune response (complete Freund's adjuvant [CFA]) in P. brasiliensis–infected mice was sufficient to break the lack of immune response to the fungus observed in infected mice. Four weeks after treatment, the CFA-treated mice presented a mild infection in the lungs characterized by preserved lung structure and small fungal burden, whereas control mice that had been treated with incomplete Freund's adjuvant presented many granulomatous lesions and high fungal burden. The immunotherapy with Th1-inducing adjuvant might be a valuable tool in the treatment of PCM and potentially useful for faster and efficient cure of PCM in humans.
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影响因子：
9.4
作者：
da Silva, SHM;Colombo, AL;de Camargo, ZP
通讯作者：
de Camargo, ZP
影响因子：
8.6
作者：
Cacere, CR;Romano, CC;Benard, G
通讯作者：
Benard, G
影响因子：
5.5
作者：
CALICH, VLG;PURCHIO, A;PAULA, CR
通讯作者：
PAULA, CR
影响因子：
2.7
作者：
Diniz, SN;Cisalpino, PS;Goes, AM
通讯作者：
Goes, AM
影响因子：
5.5
作者：
ARANGO, M;OROPEZA, F;YARZABAL, L
通讯作者：
YARZABAL, L