Expression Level Changes Of Major Outermembrane Protein Antigens Of Leptospira Interrosans During Infection And Its Regulation Mechanism

Objective To determine expression level changes of major outer membrane protein (OMP) antigens of Leptospira interrogans serogroup Icterohaemorrhagia serovar Lai strain Lai during infection of human macrophages and its regulation mechanism based on OmpR-related genes.Methods OmpR encoding genes and OmpR-related histidine kinase (HK) encoding gene of L. interrogans strain Lai and their functional domains were predicted using bioinformatic techniques. mRNA level changes of the leptospiral major OMP-encoding genes before and after infection of human THP-1macrophages were detected by real-time fluorescence quantitative RT-PCRs. Effects of the OmpR-encoding genes and HK-encoding gene to regulate the expression of leptospiral OMPs during infection were determined by HK-peptide antiserum block assay and closantel inhibitive assays.Results The bioinformatic analysis indicated that LB015and LB333were referring to OmpR-encoding genes of the spirochete, while LB014may act as the OmpR-related HK-encoding gene. After the spirochete infecting THP-1cells, mRNA levels of leptospiral lipL21, lipL32and lipL41genes were rapidly and persistently down-regulated (P<0.01), whereas mRNA levels of leptospiral groEL, mce, Ioa22and ligB genes were rapidly but transiently up-regulated (P<0.01). The treatment with closantel and HK-peptide antiserum partly reversed the infection-based down-regulated mRNA levels of lipL21and lipL48genes (P<0.01). Moreover, closantel caused a decrease of the infection-based up-regulated mRNA levels of groEL, mce, Ioa22and ligB genes (P<0.01).ConclusionsExpression levels of L. interrogans strain Lai major OMP antigens present notable changes during infection of human macrophages. There is a group of OmpR-and HK-encoding genes which may play a major role in down-regulation of expression levels of partial OMP antigens during infection.