Protective role of CCL6 during severe sepsis through interferon-γ generation and interferon-producing killer dendritic cells recruitment (44.18)

Abstract

Abstract Our group has previously demonstrated that CCL6 enhanced antimicrobial immunity during sepsis through an unknown mechanism. The goal of this study was to investigate the mechanism involved in the protective role of CCL6 during the severe sepsis. C57BL/6 transgenically overexpressing CCL6 (Tg) in the lung and wild type (WT) mice were submitted to cecal ligation and puncture (CLP) and sham operation, and survival was evaluated for up to 7 days post-CLP. Cells from peritoneal cavity (PC) were obtained 3 days after surgery. The CCL6 Tg group exhibited greater levels of CCL6 in the lung and PC when compared to WT group after sham and CLP surgery. While CCL6 Tg mice presented 90% of survival at day 7 only 20% of WT mice survived. High levels of interferon-γ (IFN-γ) were detected in the PC of CCL6 Tg mice at 3 days post-CLP. Also, cells obtained from PC of these mice produced significantly levels of IFN-γ. When CCL6 Tg mice received anti-IFN-γ prior CLP, only 20% were alive. At 3 days after sham and CLP operation, the number of natural killer (NK) cells and interferon-producing killer dendritic cells (IKDCs) was increased in the peritoneal cavity of CCL6 Tg mice when compared to WT mice. These data suggest that the protective role of CCL6 may be due to its ability to contain the consequences of an inappropriate type 2-cytokine response during anti-pathogen responses. CCL6 may achieve this through promotion of IFN-γ and NK cells and IKDCs recruitment.