Ptaquiloside from bracken (Pteridium spp.) inhibits tumour-infiltrating CD8+ T cells in HPV-16 transgenic mice. (November 2016)

• Record Type: Journal Article
• Authors: Santos, Carlos; Ferreirinha, Pedro; Sousa, Hugo; Ribeiro, Joana; Bastos, Margarida M.S.M.; Neto, Tiago; Oliveira, Paula A.; Medeiros, Rui; Vilanova, Manuel; Gil da Costa, Rui M.
• Is Part Of: Food and chemical toxicology. Volume 97(2016)
• Page Start: 277
• Page End: 285
• Publication Date: 2016-11
• Subjects: Ptaquiloside -- Human papillomavirus -- Cancer -- Bracken -- CD8+ T cells; BPV Bovine Papillomavirus -- CTL Cytotoxic T Lymphocytes -- FASL FAS Ligand -- FcγR Fragment crystallisable gamma Receptor -- H&E Haematoxylin & Eosin -- HPV Human Papillomavirus -- HSQC Heteronuclear Single Quantum Coherence spectroscopy -- IFN-γ Gamma-interferon -- K14 Keratin-14 -- LAMP1 Lysosome-associated Membrane Protein 1 -- mAb Monoclonal Antibody -- MHC Major Histocompatibility Complex -- NMR Nuclear Magnetic Resonance -- NK Natural Killer -- PTQ Ptaquiloside -- WT Wild-type; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2016.09.019
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Bracken is a fern with worldwide distribution. Exposure to bracken toxins such as ptaquiloside is hypothesized to increase the risk of papillomavirus-related cancers of the upper digestive tract. Ptaquiloside is thought to be an immunosupressor, thus allowing for the development of viral lesions. We have used a human papillomavirus type 16-transgenic (K14-HPV16) mouse model to study the effects of ptaquiloside on tumour-infiltrating CD8 + T lymphocytes, which are critical players in anti-tumour immunity. HPV16 +/− mice received ptaquiloside (0.5 mg/mouse/week) for 10 weeks. These were then euthanized at 30 weeks of age, along with age-matched untreated controls. Skin samples were enzymatically digested and CD8 + T cells analysed for CD107a and CD44 surface expression. Ptaquiloside-exposed HPV16 +/− mice showed a significantly decreased percentage (P < 0.05) of CD8 + CD107a + and CD8 + CD44 + T cells when compared with untreated HPV16 +/− animals. Histologically, 100% of ptaquilosidetreated mice showed diffuse epidermal dysplasia, compared with 50% of the untreated mice. These findings suggest that ptaquiloside exerts an immunosuppressive role by decreasing CD8 + T cell activation and degranulation in HPV-induced lesions. Given the key role of CD8 + T lymphocytes against HPV-induced lesions, this effect is likely to contribute for viral persistence, tumour progression and increased aggressiveness in patients with HPV-related malignancies. Highlights: Ptaquiloside is a suspect carcinogen that cooperates with papillomaviruses. Ptaquiloside impairs CD8 + T cell activation and degranulatory activity. This impairs the immune response against papillomavirus and cancer. Exposed papillomavirus-transgenic mice had enhanced epidermal dysplasia. Exposed populations may be at increased risk of papillomavirus-induced cancers.