RESUMO
Toll-like receptor 9 (TLR9) plays a major role in the fight against DNA viruses infections. Despite its antitumor properties, inappropriate activation of TLR9 during chronic inflammation may cause the activation of transcription factors inducing pro-cancerous activities. Thus, the relationship between TLR9 and cancer remains highly confrontational especially in gynecological cancers and cervical cancer induced by viruses. In this review, we focus on the beneficial and detrimental role of TLR9 in gynecological carcinogenesis. TLR9 contributes to tumor regression by inducing cytotoxic T cell response (CTL), reducing the numbers of myeloid-derived suppressor cells (MDSCs), the tumor-associated macrophages (TAMs) and the regulatory T cells (T regs). It can however, also promote tumor progression and invasiveness of cervical tissue. Therefore, the dichotomous role of TLR9 needs to be carefully investigated in the setting of neoplastic disease.
Assuntos
Neoplasias dos Genitais Femininos/imunologia , Proteínas de Neoplasias/fisiologia , Receptor Toll-Like 9/fisiologia , Carcinogênese , Progressão da Doença , Feminino , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Femininos/virologia , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata , Inflamação , Macrófagos/imunologia , Células Supressoras Mieloides/imunologia , NF-kappa B/metabolismo , Invasividade Neoplásica , Neovascularização Patológica/fisiopatologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/imunologia , Linfócitos T Reguladores/imunologia , Receptor Toll-Like 9/agonistasRESUMO
The protozoan parasite of the genus Leishmania has developed strategies to evade host defence mechanisms. Leishmania (L.) parasites interfere with several signalling pathways to inhibit phagocyte functions. In the present study, we analysed possible alteration of MAPK activation during infection of human U937 cell line with Leishmania major parasites. Analysis of whole cell lysates by anti-phosphotyrosine immunoblotting, showed that the pattern of tyrosine phosphorylated proteins were different for undifferentiated, PMA differentiated and Leishmania major infected cells. Cell infection induces a decrease in tyrosine phosphorylation of several host cell proteins, including PMA-induced tyrosine phosphorylated proteins. Leishmania major also caused a time dependent inhibition of ERK2 phosphorylation which correlates with the inhibition of ERK activity. This Leishmania induced effect was blocked when the cells were treated with a PTP inhibitor, prior to infection. These results suggest that Leishmania major may interfere with MAPK mediated signal transduction of the host cell through the inhibition of ERK2 activation and that this effect may be mediated by induction of protein tyrosine phosphatases activities.
