Propionibacterium acnes vaccination induces regulatory T cells and Th1 immune responses and improves mouse atopic dermatitis
ABSTRACT Atopic dermatitis (AD) is a chronic disease characterized by a polarized Th2 immune response. Propionibacterium acnes (P. acnes) has been shown to elicit strong Th1 immune responses. We hypothesized that the host immune response to P. acnes will prevent the development of AD. To demonstrate this hypothesis, we investigated the effect of P. acnes vaccination on AD that occurs in keratin 14/driven caspase-1 transgenic mouse. Vaccination with low dose of P. acnes successfully prevented clinical manifestations in the skin of AD mice associated with systemic and cutaneous increased expression of Th1-type cytokines but without suppression of Th2 cytokines. Interestingly, the numbers of IFN-γ(+) T cells, FoxP3(+) CD4(+) CD25(+) T cells (nTreg) and IL-10(+) T cells (Tr1) were significantly increased in the spleen. P. acnes vaccination has effects to alter the cytokine milieu and may be useful for the improvement of atopic symptom.
Full-textDOI: · Available from: Masato Kakeda, Sep 16, 2014
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- "In human healthy skin, an immune response is not generally mounted against commensal P. acnes. Mice can display a robust inflammatory response to P. acnes  since P. acnes bacteria do not reside naturally in the mouse skin. Although a mouse wound model recapitulated human S. aureus infection (Figure 5) and the effects of P. acnes-induced inflammatory responses on skin lesions were subtracted from controls, injection of S. aureus with glycerol into an ex vivo human skin explant  that harbors commensal P. acnes will be part of future studies. "
ABSTRACT: Bacterial interference creates an ecological competition between commensal and pathogenic bacteria. Through fermentation of milk with gut-friendly bacteria, yogurt is an excellent aid to balance the bacteriological ecosystem in the human intestine. Here, we demonstrate that fermentation of glycerol with Propionibacterium acnes (P. acnes), a skin commensal bacterium, can function as a skin probiotic for in vitro and in vivo growth suppression of USA300, the most prevalent community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). We also promote the notion that inappropriate use of antibiotics may eliminate the skin commensals, making it more difficult to fight pathogen infection. This study warrants further investigation to better understand the role of fermentation of skin commensals in infectious disease and the importance of the human skin microbiome in skin health.PLoS ONE 02/2013; 8(2):e55380. DOI:10.1371/journal.pone.0055380 · 3.23 Impact Factor
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- "The spleens were sampled and single cell suspensions was prepared by mechanical mincing, as reported previously . For the characterization of tumor infiltrating lymphocytes (TIL), skin tumor tissue from the dorsal region was removed, minced gently with scissors and then single cell suspensions were prepared. "
ABSTRACT: Malignant melanoma (MM) is an aggressive cutaneous malignancy associated with poor prognosis; many putatively therapeutic agents have been administered, but with mostly unsuccessful results. Propionibacterium acnes (P. acnes) is an aerotolerant anaerobic gram-positive bacteria that causes acne and inflammation. After being engulfed and processed by phagocytes, P. acnes induces a strong Th1-type cytokine immune response by producing cytokines such as IL-12, IFN-γ and TNF-α. The characteristic Th2-mediated allergic response can be counteracted by Th1 cytokines induced by P. acnes injection. This inflammatory response induced by P. acnes has been suggested to have antitumor activity, but its effect on MM has not been fully evaluated. We analyzed the anti-tumor activity of P. acnes vaccination in a mouse model of MM. Intratumoral administration of P. acnes successfully protected the host against melanoma progression in vivo by inducing both cutaneous and systemic Th1 type cytokine expression, including TNF-α and IFN-γ, which are associated with subcutaneous granuloma formation. P. acnes-treated tumor lesions were infiltrated with TNF-α and IFN-γ positive T cells. In the spleen, TNF-α as well as IFN-γ producing CD8+T cells were increased, and interestingly, the number of monocytes was also increased following P. acnes administration. These observations suggest that P. acnes vaccination induces both systemic and local antitumor responses. In conclusion, this study shows that P. acnes vaccination may be a potent therapeutic alternative in MM.PLoS ONE 12/2011; 6(12):e29020. DOI:10.1371/journal.pone.0029020 · 3.23 Impact Factor
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ABSTRACT: Atopic dermatitis (AD) is a recurrent inflammatory skin disease characterized by dominant T-helper (Th) 2 cytokine response. Bacillus Calmette-Guérin (BCG) has been used for preventing tuberculosis, and is regarded as a strong Th1 cytokine inducer. Antigen (Ag) 85B is a secretory protein present in Mycobacterium species that induces Th1 cytokine production. We investigated the effects of combined vaccination of heat-killed BCG (hkBCG) and Mycobacterium kansasii Ag85B in an AD mouse model. For the AD model, keratin 14 promoter-derived caspase-1 overexpressing mice (KCASP1Tg) were used. The mice received a combination therapy of hkBCG at age 3 weeks and Ag85B twice weekly for 11 weeks from the 4th week; Ag85B monotherapy from the 4th week; hkBCG monotherapy at the 3rd week; or control saline. Areas of skin lesions, cytokine mRNA expression and serum interleukin (IL)-18 and immunoglobulin (Ig) E levels were analysed. Inducible Foxp3+ regulatory T cells (iTreg), IL-10-producing T cells (Tr1), and interferon (IFN)-γ/IL-4/IL-17-producing T cells were evaluated in the spleen. Saline-treated mice and hkBCG monotherapy mice spontaneously developed severe dermatitis. However, combined therapy with hkBCG and Ag85B significantly suppressed the development of skin lesions and mast cell infiltrations. Elevations of the serum IgE and IL-18 levels were significantly suppressed with combined therapy. Mice treated with hkBCG and Ag85B had a normal number of iTreg in the spleen, and decreased number of both IL-4- and IL-17-producing CD4+ T cells. The effect of Ag85B monotherapy was limited. Combined vaccination with hkBCG and Ag85B decreases AD skin lesions by inducing regulatory T cells, suggesting that this vaccination is a potent and novel therapeutic strategy for AD.British Journal of Dermatology 12/2011; 166(5):953-63. DOI:10.1111/j.1365-2133.2011.10763.x · 4.10 Impact Factor