Celada, Antonio

Inflammation is the response of the immune system to all types of injuries: infection, trauma, physical or chemical agents, etc. Macrophages are the cells of the immune system with major plasticity controlling a large number of cells and different pathways. They are also the hinge between natural and acquired immunity. Our objectives are the following: 1) Mechanisms of macrophage survival during inflammation. Macrophages produce a large number of toxic products that may affect the viability of these cells and to be protected they express several mechanisms such as nucleases or other molecules, 2) Role of Ly-6Chigh monocytes in inflammation, these cells are created in the bone marrow and move specifically to the inflammatory loci. Our group can differentiate these cells in vitro and we can modified to know the mechanisms involved in inflammation, 3) Role of mitochondria on macrophages functional activity, and in special of mitofusin-2, and 4) Macrophaging, or the modifications in macrophages by aging. Our studies involve molecular biology, cellular biology, biochemical determinations and in vivo models. Inflammation occurs when the body suffers aggression either by microbes, trauma or a variety of physical agents, such as heat, radiation, etc.

Inflammation is also involved in the pathogenesis of chronic diseases of autoimmune origin (eg rheumatoid arthritis and diabetes) and cancer. In the early stages of inflammation, there is an increase in the size of the vessels around the inflammatory loci and the release of liquids. After, distinct cells reach these loci in a highly specific order: in the first 24 h neutrophils, at 48 h macrophages, and several days later lymphocytes. Neutrophils kill most types of microbes. In the initial stages of inflammation, macrophages eliminate the remaining microbes that escape the neutrophils, remove the apoptotic bodies of dead neutrophils and present antigen to T-lymphocytes, thereby initiating the mechanisms of acquired immunity, which ends in the production of antibodies and cytokines and memory cells, the latter a key element for the vaccines. Macrophage activity then switches from being pro-inflammatory to anti-inflammatory, whereby they remove all the tissue debris, thus achieving healing. Our project is the continued work of many years devoted to the biology of macrophages and dendritic cells. These cell types play a key role in the innate immune response and form a bridge between the innate and acquired response.