The protein S100A9 plays a key role in the control of inflammatory response. The C-terminus of the murine S100A9 protein (mS100A9p) downregulates the spreading and phagocytic activity of adherent peritoneal cells. Murine peritoneal cells are constituted by macrophages and B-1 cells, and the latter exert an inhibitory effect on macrophage functions by secreting interleukin- (IL-) 10. Here, we investigated the influence of B-1 cells on the inhibitory effect evoked by mS100A9p on macrophages. mS100A9p did not alter spreading and phagocytosis either by peritoneal macrophages obtained from mice deprived of B-1 cells or by bone marrow-derived macrophages (BMDMϕ). Nevertheless, when BMDMϕ were cocultivated by direct or indirect contact with B-1 cells treated with mS100A9p, the phagocytosis by BMDMϕ was decreased, showing that the effect of mS100A9p on macrophages was modulated by B-1 cells and/or their secretory compounds. Furthermore, the inhibitory action of mS100A9p on phagocytosis by adherent peritoneal cells was abolished in cells obtained from IL-10 knockout mice. Taken together, the results show that mS100A9p has no direct inhibitory effect on macrophages; however, mS100A9p modulates B-1 cells, which in turn downregulates macrophages, at least in part, via IL-10. These data contribute to the characterization of S100A9 functions involving B-1 cells in the regulation of the inflammatory process.

Cervical intraepithelial neoplasia has a high incidence in many of the world's populations, and it has been hypothesized to be a precursor of uterine cervical cancer. Cervical intraepithelial neoplasia also shares similar pathological traits with human papillomavirus infections. Various surgical treatments have been proposed over the years for the treatment of cervical intraepithelial neoplasia, including conization, hysterectomy and, more recently, a loop electrosurgical excisional procedure. However, a higher recurrence rate of the disease has been observed after these procedures. Therefore, immunotherapy has been proposed as a potential treatment to be used in conjunction with surgery, or independently, as treatment for cervical intraepithelial neoplasia. Currently, immunotherapy includes the application of recombinant viral proteins, vaccines, or antibody-and dendritic cell-based therapies. In this review, we summarize the development and testing of these immunotherapy approaches, particularly in regard to their application for the treatment of cervical intraepithelial neoplasia.