title: TLR4 and TLR9 signals stimulate protective immunity against blood-stage Plasmodium yoelii infection in mice.
abstract: The mechanisms regulating the induction of protective immunity against blood-stage malaria remain unclear. Resistant DBA/2 mouse develops a higher Th1 response compared with a susceptible BALB/c strain during Plasmodium yoelii (Py) infection. It is known that the T helper cell response is initiated and polarized by dendritic cells (DCs) of the innate immune system, during which TLR4 and TLR9 are important receptors for the innate recognition of the malaria parasite and its products. We hypothesized that TLR4/9 may play critical roles in the induction of protective immunity against Py infection. We used TLR4/9 antagonists and agonists to study their effects on mouse resistance to Py infection. We found that the administration of an antagonist prior to infection aggravated disease outcomes, impaired DC functions and suppressed the pro-inflammatory response to Py infection in resistant DBA/2 mice. Treatment with the TLR4 agonist lipopolysaccharide (LPS) but not TLR9 agonist significantly improved the survival rate of susceptible Py-infected BALB/c mice. LPS administration promoted the activation and expansion of DCs and drove a Th1-biased response. Our data demonstrate the important roles of TLR4/9 signals in inducing resistance to malaria parasites and provide evidence for the rational use of TLR agonists to potentiate protective immunity against Plasmodium infection.
authors.affiliation: Department of Immunology, Basic Medicine College of China Medical University, Shenyang 110001, China; Medical Examination Center, The First Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Basic Medicine College of China Medical University, Shenyang 110001, China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Immunology, Basic Medicine College of China Medical University, Shenyang 110001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Pang
authors.affiliation: Department of Immunology, Basic Medicine College of China Medical University, Shenyang 110001, China.
authors.forename: Zanmei
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Department of Entomology, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Liwang
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Immunology, Basic Medicine College of China Medical University, Shenyang 110001, China. Electronic address: ymcao@mail.cmu.edu.cn.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology; D010967:Plasmodium yoelii / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: C423449:CpG ODN 1826; D016207:Cytokines; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Adaptive immunity; Innate immunity; Malaria; Plasmodium yoelii; TLR4; TLR9