Toll-Like Receptor 2 Agonist Pam3CSK4 Alleviates the Pathology of Leptospirosis in Hamster.
Leptospirosis, caused by pathogenic spirochetes, is a zoonotic disease of global importance. The detailed pathogenesis of leptospirosis is still unclear, which limits the ideal treatment of leptospirosis. In this study, we analyzed the expression of Toll-like receptor 2 (TLR2) and TLR4 in target organs of both resistant mice and susceptible hamsters after Leptospira interrogans serovar Autumnalis infection. TLR2 but not TLR4 transcripts in mouse organs contrasted with delayed induction and overexpression in hamster organs. Coinjection of leptospires and the TLR2 agonist Pam3CSK4 into hamsters improved their survival rate, alleviated tissue injury, and decreased the abundance of leptospires in target organs. The production of interleukin-10 (IL-10) from tissues was enhanced in hamsters of the group coinjected with leptospires and Pam3CSK4 compared with the leptospira-injected group. Similarly, IL-10 levels in TLR2-deficient mice were lower than those in wild-type mice. A high ratio of IL-10/tumor necrosis factor alpha (TNF-α) levels was found in both infected wild-type mice and hamsters coinjected with leptospires and Pam3CSK4. Moreover, TLR2-dependent IL-10 expression was detected in peritoneal macrophages after leptospira infection. Our data demonstrate that coinjection of leptospires and Pam3CSK4 alleviates the pathology of leptospirosis in hamsters; this effect may result from the enhanced expression of TLR2-dependent IL-10.
Department of Clinical Science, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China.
Wenlong
W
Zhang
Department of Clinical Science, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China.
Naisheng
N
Zhang
Department of Clinical Science, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China.
Xufeng
X
Xie
Department of Clinical Science, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China.
Jian
J
Guo
Department of Clinical Science, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China.
Xuemin
X
Jin
Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.
Feng
F
Xue
Department of Infectious Disease, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China dingzhuang@jlu.edu.cn ygcao82@jlu.edu.cn.|Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China.
Zhuang
Z
Ding
Department of Clinical Science, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China dingzhuang@jlu.edu.cn ygcao82@jlu.edu.cn.|Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China.
Yongguo
Y
Cao
D000818:Animals; D006224:Cricetinae; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007921:Leptospira interrogans; D007922:Leptospirosis / Q000188:drug therapy* / Q000473:pathology; D055666:Lipopeptides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016753:Interleukin-10