Bastilho Alexandre Lazoski, Brito Ramayana M M, Andrade José L, da Rocha Rihs José Bryan, de Brito Duval Isabela, Cardozo Marcelo Eduardo, Antunes Porto Ana Rafaela, do Amaral Luisa Braga, Nascimento Souza Jorge Lucas, Cassali Geovanni Dantas, Melo Brena K C, Lemos Jully Anne B, Cavalcante Rômulo S, Bueno Lilian, Fujiwara Ricardo Toshio, Souto Janeusa T, Magalhães Luisa M D, Andrade-Neto Valter Ferreira
Department of Microbiology and Parasitology, Biosciences Center, Federal University of Rio Grande do Norte, Natal, Brazil.
Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Parasitology. 2025 Apr;152(5):497-509. doi: 10.1017/S0031182025000538.
non-archetypal strains have distinct virulence profiles and immunological activation in the host when compared with archetypal strains. The present work aims to perform an analysis of the inflammatory profile during acute and early chronic infection by atypical strain in an experimental murine model. After euthanasia, blood was collected for the quantification of specific IgG antibodies and their subtypes (IgG1/IgG3) by ELISA; bronchoalveolar lavage (BAL) was realized and immunophenotyping of lymphocytes population was performed at 12- and 30-days post infection (dpi); the levels of IFN-γ, IL-12, IL-10, TNF-α, IL-6, IL-17, nitric oxide and total proteins were determined in the BAL supernatant. Tissue cyst burden was determined in the brain homogenate, and the parasite load in the lungs was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Infection with the CK4 strain induced a lower brain cyst load similar parasite burden in the lungs, and higher levels of IgG1 and IgG3, when compared to ME49. The group infected with the CK4 strain presented higher levels of systemic IFN-γ, and both infected groups displayed similarly elevated levels of systemic TNF-α, IL-6 and IL-17 at 30 dpi, as well as higher numbers of CD4 and CD8 T lymphocytes in the acute stage of infection, followed by higher numbers of central and effector CD4 T cells. IFN-γ levels in the BAL fluid were significantly higher in animals infected with the CK4 strain in both the acute and early chronic stage of infection, highlighting the involvement of the lung environment.
与原型菌株相比,非原型菌株在宿主体内具有独特的毒力特征和免疫激活情况。本研究旨在通过实验小鼠模型分析非典型菌株在急性和早期慢性感染期间的炎症特征。安乐死后,采集血液通过酶联免疫吸附测定(ELISA)定量特异性IgG抗体及其亚型(IgG1/IgG3);进行支气管肺泡灌洗(BAL),并在感染后12天和30天对淋巴细胞群体进行免疫表型分析;测定BAL上清液中IFN-γ、IL-12、IL-10、TNF-α、IL-6、IL-17、一氧化氮和总蛋白的水平。测定脑匀浆中的组织囊肿负荷,并通过定量逆转录聚合酶链反应(qRT-PCR)评估肺部的寄生虫负荷。与ME49相比,感染CK4菌株导致较低的脑囊肿负荷、肺部相似的寄生虫负荷,以及更高水平的IgG1和IgG3。感染CK4菌株的组在30 dpi时呈现较高水平的全身IFN-γ,两个感染组在30 dpi时全身TNF-α、IL-6和IL-17水平均同样升高,并且在感染急性期CD4和CD8 T淋巴细胞数量较多,随后中央和效应CD4 T细胞数量增加。在感染的急性和早期慢性阶段,感染CK4菌株的动物BAL液中的IFN-γ水平显著更高,突出了肺部环境的参与。