Corynebacterium pyruviciproducens promotes the production of ovalbumin specific antibody via stimulating dendritic cell differentiation and up-regulating Th2 biased immune response
Highlights
► C. pyruviciproducens effectively induced proliferation, activation of dendritic cells. ► C. pyruviciproducens promoted antigen-specific humoral immune response. ► C. pyruviciproducens may be used as a bacterial adjuvant.
Introduction
In recent years, a growing number of researchers are showing interest in bacterial adjuvants and many bacterial components are being developed to circumvent unsafe effects [1]. Propionibacterium acnes is a typical bacterial immunomodulator and has been used to treat several kinds of cancers [2], [3], [4]. Lately, some active components isolated from P. acnes are developed as a new immunomodulator [5].
Corynebacterium pyruviciproducens is a newly discovered Corynebacterium species without known pathogenic components such as diphtheria toxin and tuberculostearic acid [6] that has similar biological properties to P. acnes. Meanwhile, C. pyruviciproducens showed a strong ability to induce antibody production in our previous experiments, and it aroused our interest in the immunoregulation of C. pyruviciproducens compared with P. acnes.
Dendritic cells (DCs) play a crucial role in connecting inherent immunity with adaptive immunity and are key players in activation of the adaptive immune system owing to their antigen presentation ability and priming of T cells [7]. DCs also express co-stimulation molecules and secrete several cytokines which efficiently activate T and B lymphocytes. Numerous studies have validated that DCs, capable of modulating both cellular and humoral immune responses, can be considered as effective regulator for studying bacteria-based immunostimulatory effects.
In this study, D2SC/1 cell line and BMDC were chosen to investigate the effect of C. pyruviciproducens on immunomodulation in vitro, and the stimulatory function of C. pyruviciproducens on dendritic cells was analyzed by detecting the levels of cytokine-secretion, ability of cell-proliferation and expression of membrane molecules. Furthermore, the effect of C. pyruviciproducens on promoting antibody production in mice was detected. It is hoped to develop a new bacterial adjuvant with higher power of regulating immune response.
Section snippets
Bacterial strains
P. acnes (ATCC6919, obtained from Guangdong Culture Collection Center, China) was cultured in Lysogeny broth (LB) medium in an anaerobic jar at 37 °C for 3 days; C. pyruviciproducens (CCUG 57046, obtained from Olive View Medicine Center, University of California, USA) was cultured in LB medium with 5% new-born calf serum (NCS) (Sigma, USA) at 37 °C for 3 days. Collected bacteria were washed three times by centrifugation (12,000 rpm, 10 min). The bacterial pellet was re-suspended in sterile saline
C. pyruviciproducens induced D2SC/1 and BMDC to produce more inflammatory cytokine secretions than P. acnes
mRNA levels (Fig. 1) and protein level (Fig. 2) of IL-6 and IL-12p40 secreted by D2SC/1 and BMDC were analyzed. Increasing amounts of IL-6 and IL-12p40 mRNA were found following growth with stimulating concentrations of both C. pyruviciproducens and P. acnes; however, C. pyruviciproducens showed a stronger influence in inducing cytokine expression than P. acnes (Fig. 1). ELISA results showed that D2SC/1 and BMDC responded to C. pyruviciproducens in a dose-responsive manner (100; 500; 1000 μg/ml)
Discussion
In this study, C. pyruviciproducens was verified in vitro as an active immunostimulatory adjuvant which enhanced secretion of IL-6, a potent Th2-biased inflammatory cytokine [12] and IL-12, a Th1 specific cytokine [13]. The effects of C. pyruviciproducens on DCs may be due to complex bacterial compositions like CpG oligonucleotides (ligand of TLR9), peptidoglycan and teichoic acid [14].
Our data also showed that C. pyruviciproducens was much capable of significantly promoting proliferation on
Acknowledgements
This work was supported by the National Natural Science Foundation of China (30871193, 30972748, 81101227), the Natural Science Foundation of Colleges and Universities in Jiangsu Province and Innovation Fund for candidate of doctor in Jiangsu Province (Grant nos. 09KJB310001 and CX09B_217Z, respectively).
References (24)
- et al.
The introduction of multi-copy CpG motifs into an antiviral DNA vaccine strongly up-regulates its immunogenicity in fish
Vaccine
(2011) - et al.
Non-cell Corynebacterium parvum generated by nanotechnology: a promising immunomodulator with less side effects
Int Immunopharmacol
(2007) Role of interleukin-12 family cytokines in the cellular response to mycobacterial disease
Int J Infect Dis
(2010)- et al.
Immunology of TLR-independent vaccine adjuvants
Curr Opin Immunol
(2009) Overview of vaccine adjuvants: present and future
Vaccine
(2002)- et al.
Modulation of the type I hypersensitivity late phase reaction to OVA by Propionibacterium acnes-soluble polysaccharide
Immunol Lett
(2008) - et al.
Development of novel lipidated analogs of picroside as vaccine adjuvants: acylated analogs of picroside-II elicit strong Th1 and Th2 response to ovalbumin in mice
Vaccine
(2010) - et al.
Harmful effects of i.v. Corynebacterium parvum given at the same time as cyclophosphamide in patients with squamous-cell carcinoma of the bronchus
Br J Cancer
(1980) - et al.
Lower relapse rates after neighbourhood injection of Corynebacterium parvum in operable cervix carcinoma
Br J Cancer
(1981) - et al.
Comparison of the effectiveness of some pleural sclerosing agents used for control of effusions in malignant pleural mesothelioma: a review of 117 cases
Respiration
(2000)
Corynebacterium pyruviciproducens sp nov., a pyruvic acid producer
Int J Syst Evol Microbiol
Dendritic cell maturation by innate lymphocytes: coordinated stimulation of innate and adaptive immunity
J Exp Med
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These authors contributed equally to this work.