Wang Mei-lian, Feng Yong-hui, Pang Wei, Qi Zan-mei, Zhang Ying, Guo Ya-jun, Luo En-jie, Cao Ya-ming
Department of Immunology, College of Basic Medical Sciences, China Medical University, No 92 Beier Road, Heping District, Shenyang 110001, China.
Malar J. 2014 Mar 26;13:116. doi: 10.1186/1475-2875-13-116.
Malaria and schistosomiasis are endemic and co-exist in the same geographic areas, even co-infecting the same host. Previous studies have reported that concomitant infection with Schistosoma japonicum could offer protection against experimental cerebral malaria (ECM) in mice. This study was performed to evaluate whether alterations in parasite density could alter this protective effect.
Mice were inoculated with 100 or 200 S. japonicum cercariae followed by infection with high or low density of Plasmodium berghei ANKA strain eight weeks after the first infection. Then, parasitaemia, survival rate and blood-brain-barrier (BBB) damage were assessed. Interferon-gamma (IFN-γ), interleukin (IL)-4, IL-5, IL-13, IL-10, and TGF-β levels were determined in splenocyte supernatants using enzyme-linked immunosorbent assay (ELISA). Cell surface/intracellular staining and flow cytometry were used to analyse the level of CD4(+)/CD8(+) T cells, CD4(+)CD25(+)Foxp3(+) Tregs, IL-10-secreting Tregs, and IL-10(+)Foxp3-CD4(+) T cells in the spleen, and CD4(+)/CD8(+) T cells infiltrating the brain.
Co-infection with low density P. berghei and increased S. japonicum cercariae significantly increased the levels of IL-4, IL-5, IL-13, TGF-β and Tregs, but significantly decreased the levels of IFN-γ and the percentage of CD4(+) T cells and CD8(+) T cells in the spleen and CD8(+) T cell infiltration in the brain. Increased worm loads also significantly decreased mortality and BBB impairment during ECM. When challenged with higher numbers of P. berghei and increased cercariae, the observed cytokine changes were not statistically significant. The corresponding ECM mortality and BBB impairment also remained unchanged.
This study demonstrates that protection for ECM depends on the numbers of the parasites, S. japonicum and P. berghei, during co-infection. Alterations in the regulatory response appear to play a key role in this adaptation.
疟疾和血吸虫病在同一地理区域流行且共存，甚至可共同感染同一宿主。既往研究报道，日本血吸虫合并感染可对小鼠实验性脑型疟疾（ECM）起到保护作用。本研究旨在评估寄生虫密度的改变是否会改变这种保护作用。
给小鼠接种100或200条日本血吸虫尾蚴，首次感染8周后再用低密度或高密度伯氏疟原虫ANKA株进行感染。然后，评估疟原虫血症、存活率和血脑屏障（BBB）损伤情况。采用酶联免疫吸附测定（ELISA）法测定脾细胞上清液中干扰素-γ（IFN-γ）、白细胞介素（IL）-4、IL-5、IL-13、IL-10和转化生长因子-β（TGF-β）的水平。运用细胞表面/细胞内染色和流式细胞术分析脾脏中CD4(+)/CD8(+) T细胞、CD4(+)CD25(+)Foxp3(+)调节性T细胞（Tregs）、分泌IL-10的Tregs以及IL-10(+)Foxp3-CD4(+) T细胞的水平，以及浸润大脑的CD4(+)/CD8(+) T细胞水平。
低密度伯氏疟原虫与增多的日本血吸虫尾蚴合并感染显著增加了IL-4、IL-5、IL-13、TGF-β和Tregs的水平，但显著降低了IFN-γ水平以及脾脏中CD4(+) T细胞和CD8(+) T细胞的百分比，还有大脑中CD8(+) T细胞的浸润。虫负荷增加还显著降低了ECM期间的死亡率和BBB损伤。当用更多数量的伯氏疟原虫和增多的尾蚴进行攻击时，观察到的细胞因子变化无统计学意义。相应的ECM死亡率和BBB损伤也保持不变。
本研究表明，对ECM的保护作用取决于合并感染期间日本血吸虫和伯氏疟原虫的数量。调节反应的改变似乎在这种适应性变化中起关键作用。
