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Synergistic effect of muramyl dipeptide with heat shock protein 70 from Mycobacterium tuberculosis on immune activation

 Tae-Hyoun Kim  ;  Jong-Hwan Park  ;  Yeong-Min Park  ;  Seung-Wook Ryu  ;  Sung Jae Shin  ;  Jae-Hak Park  ;  Dong-Jae Kim 
 IMMUNOBIOLOGY, Vol.220(1) : 26-31, 2015 
Journal Title
Issue Date
Acetylmuramyl-Alanyl-Isoglutamine/immunology* ; Acetylmuramyl-Alanyl-Isoglutamine/pharmacology ; Animals ; Antigen-Presenting Cells/drug effects ; Antigen-Presenting Cells/immunology ; Bacterial Proteins/immunology* ; Bacterial Proteins/pharmacology ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; Chemokines/biosynthesis ; Cytokines/biosynthesis ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Disease Models, Animal ; Endocytosis/immunology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; HSP70 Heat-Shock Proteins/immunology* ; HSP70 Heat-Shock Proteins/pharmacology ; Humans ; Mice ; Mice, Knockout ; Mycobacterium tuberculosis/immunology* ; Mycobacterium tuberculosis/metabolism ; NF-kappa B/metabolism ; Tuberculosis/immunology ; Tuberculosis/metabolism
Dendritic cells ; Heat shock protein 70 ; Immune activation ; Muramyl dipeptide ; Mycobacterium tuberculosis
Heat shock protein 70 from Mycobacterium tuberculosis (Mtb Hsp70) has been known to modulate immune response including dendritic cell activation. Muramyl dipeptide (MDP) is an immunoreactive derivative of peptidoglycan from all Gram-negative and Gram-positive bacteria and recognized to be responsible for function of Freund's complete adjuvant. In this study, we evaluated effect of MDP on in vitro activation of bone marrow derived dendritic cells (BMDCs) and in vivo production of cytokines and chemokines induced by Mtb Hsp70. MDP treatment with Mtb Hsp70 dramatically increased production of IL-6, IL-12p40 and TNF-α in BMDCs compared with Mtb Hsp70 alone whereas these effects were abolished in Nod2-deficient BMDCs. Phosphorylation of IκB-α and ERK and impairment of phagocytosis, which is an indicator of DC maturation were enhanced by MDP co-treatment with Mtb hsp70 in BMDCs. In addition, ability of Mtb Hsp70-stimulated BMDCs to induce IFN-γ productions of T cells was increased by MDP co-treatment. Finally, intraperitoneal injection of MDP with Mtb Hsp70 dramatically increased production of IL-6, CXCL-1 and CCL2 in serum compared with Mtb hsp70 injection. Our study showed the synergistic effects of MDP with Mtb Hsp70 on DCs and in vivo immune activation. The use of MDP with Mtb Hsp70 to induce immune activation may provide an effective strategy for vaccination to treat cancer and protect against pathogens.
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1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Shin, Sung Jae(신성재) ORCID logo https://orcid.org/0000-0003-0854-4582
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