Identification and functional characterization of Oncomelania hupensis macrophage migration inhibitory factor involved in the snail host innate immune response to the parasite Schistosoma japonicum.
Schistosomiasis, caused by parasitic trematodes of the genus Schistosoma, remains a devastating public health problem, with over 200 million people infected and 779 million people at risk worldwide, especially in developing countries. The freshwater amphibious snail Oncomelania hupensis is the obligate intermediate host of Schistosoma japonicum. This unique and long-standing host-parasite interaction highlights the biomedical importance of the molecular and cellular mechanisms involved in the snail immune defense response against schistosome infection. In recent years, a number of immune-related effectors and conserved signalling pathways have been identified in molluscs, especially in Biomphalaria glabrata, which is an intermediate host for Schistosoma mansoni, but few have been reported in O. hupensis. Here we have successfully identified and functionally characterized a homologue of mammalian macrophage migration inhibitory factor (MIF) from O. hupensis (OhMIF). MIF, a pleiotropic regulator of innate immunity, is a constitutively expressed mediator in the host's antimicrobial defense system and stress response that promotes the pro-inflammatory functions of immune cells. In the present study, we detected the distribution of OhMIF in various snail tissues, especially in immune cell types (hemocytes) and found that OhMIF displays significantly increased expression in snails following challenge with S. japonicum. Knockdown of OhMIF was conducted successfully in O. hupensis and significantly reduced the percentage of phagocytic cell populations in circulating hemocytes. Furthermore, OhMIF is not only implicated in the activation and differentiation of hemocytes, but also essential to promote the migration and recruitment of hemocytes towards the infected sites. These results provide the first known functional evidence in exploring the molecular mechanisms involved in the O. hupensis innate immune defense response to the parasite S. japonicum and help to better understand the complex host-parasite interaction.
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China; Parasitology Research Laboratory, School of Life Sciences, Xiamen University, Xiamen, Fujian, China. Electronic address: huangshuaiqin@foxmail.com.
Shuaiqin
S
Huang
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China; Parasitology Research Laboratory, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Yunchao
Y
Cao
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China; Parasitology Research Laboratory, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Mingke
M
Lu
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China; Parasitology Research Laboratory, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Wenfeng
W
Peng
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Key Laboratory of Animal Parasitology, Ministry of Agriculture of China, Shanghai, China.
Jiaojiao
J
Lin
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China; Parasitology Research Laboratory, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Chongti
C
Tang
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China; Parasitology Research Laboratory, School of Life Sciences, Xiamen University, Xiamen, Fujian, China. Electronic address: liang.tang@bayer.com.
Liang
L
Tang
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D005786:Gene Expression Regulation / Q000276:immunology; D055785:Gene Knockdown Techniques; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology*; D008958:Models, Molecular; D010587:Phagocytosis; D010802:Phylogeny; D011487:Protein Conformation; D060888:Real-Time Polymerase Chain Reaction; D012549:Schistosoma japonicum / Q000502:physiology*; D012908:Snails / Q000276:immunology / Q000469:parasitology*
D008263:Macrophage Migration-Inhibitory Factors
Circulating hemocytes; Innate immune response; MIF cytokine; Oncomelania hupensis; Schistosoma japonicum