Fish lymphocytes regulate the inflammatory response via the production of chemokines (94.24)

Abstract

Abstract Macrophages provide the first line of defense against infections through the recognition of different pathogen-associated molecular patterns (PAMPs). Upon activation, they produce pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα), which regulate not only innate but also adaptive immunity. In the bony fish gilthead seabream, we have shown that TNFα produced by activated macrophages induces the recruitment and activation of professional phagocytic granulocytes when injected intraperitoneally, but it hardly activates these cells in vitro. In this study, we report that seabream TNFα is able to up-regulate the expression of E-selectin in endothelial cells, leading to a concomitant increased adhesion of activated granulocytes and lymphocytes. More importantly, although all fish immune cell types analyzed, i.e. granulocytes, macrophages and lymphocytes, produce the CCL4-like chemokine in response to different PAMPs, only lymphocytes and endothelial cells are able to produce this chemokine in response to TNFα. These results demonstrate that TNFα in fish is mainly involved in the recruitment of leukocytes to the inflammatory foci rather than in their activation and suggest a role for fish lymphocytes in the regulation of early immune responses to infection. This work was supported by the Spanish Ministry of Education and Science (grant BIO2005-05078) and the Sixth Framework Programme of the European Union (grant SSP8-CT-2003-501984).