Ostertagia ostertagi macrophage migration inhibitory factor is present in all developmental stages and may cross-regulate host functions through interaction with the host receptor

Authors

Guanggang Qu, Agricultural Research Service, USDA & Shangdong Binzhou Academy of Animal Science and Veterinary Medicine, Binzhou City
Raymond Fetterer, Agricultural Research Service, USDA
Lin Leng, Yale University School of Medicine, New Haven
Xin Du, Yale University School of Medicine, New Haven
Dante Zarlenga, Agricultural Research Service, USDA
Zhiqiang Shen, hangdong Binzhou Academy of Animal Science and Veterinary Medicine, Binzhou City
Wenyu Han, Jilin University, Changchun
Richard Bucala, Yale University School of Medicine, New Haven
Wenbin Tuo, Agricultural Research Service, USDAFollow

Date of this Version

2-28-2014

Citation

U.S. Government Works

Comments

http://dx.doi.org/10.1016/j.ijpara.2014.01.009

G. Qu et al. / International Journal for Parasitology 44 (2014) 355–367

Abstract

Macrophage migration inhibitory factor (MIF) of Ostertagia ostertagi, an abomasal parasite of cattle, was characterised in the present study. Phylogenetic analysis identified at least three O. ostertagi MIFs (Oos- MIFs), each encoded by a distinct transcript: Oos-MIF-1.1, Oos-MIF-1.2 and Oos-MIF-2. Oos-MIF-2 is only distantly related to Oos-MIF-1s, but has higher sequence similarity with the Caenorhabditis elegans MIF2. Oos-MIF-1.1 and Oos-MIF-1.2 are similar (93%) and thus collectively referred to as Oos-MIF-1 when characterised with immunoassays. Recombinant Oos-MIF-1.1 (rOos-MIF-1.1) is catalytically active as a tautomerase. A mutation (rOos-MIF-1.1P1G) or duplication of Pro1 residue (rOos-MIF-1.1P1+P) resulted in reduced oligomerisation and loss of tautomerase activity. The tautomerase activity of rOos-MIF-1.1 was only partially inhibited by ISO-1 but was abrogated by a rOos-MIF-1.1-specific antibody. Oos-MIF- 1 was detected in all developmental stages of O. ostertagi, with higher levels in the adult stage; it was also detected in adult worm excretory/secretory product. Oos-MIF-1 was localised to the hypodermis/muscle, reproductive tract and intestine, but not to the cuticle. rOos-MIF-1.1, but not rOos-MIF-1.1P1G, was able to specifically bind to human CD74, a MIF cell surface receptor, with an affinity comparable with human MIF. Immunostaining indicated that macrophages were able to internalise rOos-MIF-1.1, further supporting receptor-mediated transportation. Herein we also show that rOos-MIF-1.1 inhibited migration of bovine macrophages and restored glucocorticoid-suppressed, lipopolysaccharide-induced TNF-a and IL-8 in human and/or bovine macrophages. Given its dual role in self-regulation and molecular mimicry, this secreted parasite protein warrants investigation as a vaccine candidate against O. ostertagi infections in cattle.