Characterization of Plasmodium berghei Homologues of T-cell Immunomodulatory Protein as a New Potential Candidate for Protecting against Experimental Cerebral Malaria

• Published in: Korean journal of parasitology Vol. 57; no. 2; pp. 101 - 115
• Main Authors: Cui, Ai, Li, Yucen, Zhou, Xia, Wang, Lin, Luo, Enjie
• Format: Journal Article
• Language: English
• Published: Korea (South) 대한기생충학열대의학회 01.04.2019; The Korean Society for Parasitology and Tropical Medicine
• Subjects: Administration, Intravenous; Animals; Brain - pathology; Disease Models, Animal; Endothelial Cells - drug effects; Immunologic Factors - administration & dosage; Immunologic Factors - isolation & purification; Lymphocyte Activation; Malaria, Cerebral - pathology; Malaria, Cerebral - prevention & control; Membrane Proteins - administration & dosage; Membrane Proteins - genetics; Membrane Proteins - isolation & purification; Mice, Inbred BALB C; Mice, Inbred C57BL; Original; Plasmodium berghei - genetics; Plasmodium berghei - immunology; Protozoan Proteins - administration & dosage; Protozoan Proteins - genetics; Protozoan Proteins - isolation & purification; Recombinant Proteins - administration & dosage; Recombinant Proteins - genetics; Recombinant Proteins - isolation & purification; T-Lymphocytes, Regulatory - drug effects; Treatment Outcome; T-cell immunomodulatory protein; Plasmodium berghei; inflammatory cytokine; experimental; immunopathology; cerebral malaria
• ISSN: 0023-4001; 1738-0006; 1738-0006
• DOI: 10.3347/kjp.2019.57.2.101

The pathogenesis of cerebral malaria is biologically complex and involves multi-factorial mechanisms such as microvascular congestion, immunopathology by the pro-inflammatory cytokine and endothelial dysfunction. Recent data have suggested that a pleiotropic T-cell immunomodulatory protein (TIP) could effectively mediate inflammatory cytokines of mammalian immune response against acute graft-versus-host disease in animal models. In this study, we identified a conserved homologue of TIP in Plasmodium berghei (PbTIP) as a membrane protein in Plasmodium asexual stage. Compared with PBS control group, the pathology of experimental cerebral malaria (ECM) in rPbTIP intravenous injection (i.v.) group was alleviated by the downregulation of pro-inflammatory responses, and rPbTIP i.v. group elicited an expansion of regulatory T-cell response. Therefore, rPbTIP i.v. group displayed less severe brain pathology and feverish mice in rPbTIP i.v. group died from ECM. This study suggested that PbTIP may be a novel promising target to alleviate the severity of ECM.