Macrophage Biology Group
Recently, an inflammatory component has been detected in a large number of chronic diseases such as cancer, metabolic disease, autoinmmunity, etc. It is for this reason that the field of inflammation and macrophages has been reviewed extensively during the last years in top journals (1-8) and to propose new therapeutic targets. Inflammation occurs when the body suffers aggression by either 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 24h neutrophils, at 48h 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.
During the initial steps, these cells shows a pro-inflammatory activity (M1 or classically activated), destroying the remaining microorganisms, that has not been eliminated by the neutrophils, and phagocyte the apoptotic bodies of neutrophils as well as the cells damaged in the tissues (9). After this phase, the phenotype of macrophages switches and the tissues are repaired. These anti-inflammatory macrophages, also called M2 or alternatively activated, induce the wound healing process (10). Under physiological conditions, there is a balance between the pro- and anti-inflammatory phases, but an excess of pro-inflammation could be the base for a chronic inflammation while an excess of anti-inflammation may produce an excess of fibrosis. Both excess will develop pathological processes. Therefore the control of macrophage activation in inflammation is critical.
There are two groups of macrophages that are generated in bone marrow and they arrive to all the tissues through the blood. These monocytes are functionally different and can be differentiated by their surface markers. Under normal conditions, monocytes show the phenotype Ly-6C-CD43++ in mice and CD14-CD16++ in humans (11). These cells are located around the vessels “patrolling” and if they detect an injury they move to the tissues (12). In case an inflammatory process is produced, some monocytes produced in the bone marrow that express the phenotype Ly-6C++CD43- in mice and CD14++CD16- in humans (11) are recruited at the inflammatory loci and under the effect of cytokines or bacterial products they become activated.
The knowing of these mechanisms could provide therapeutic targets to modulate the activity of macrophages during acute or chronic inflammation (13). Our project is the continued work of many years devoted to the biology of macrophages. These cell types play a key role in the innate immune response and form a bridge between the innate and acquired response. The main objective of our laboratory is to know the mechanisms controlling genomic instability occurring through macrophage activation (inflammation) and during aging. Our studies involve a large number of techniques including molecular biology, cellular biology, biochemical determinations and in vivo models.
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7. Tur J, Vico T, Lloberas J, Zorzano A, Celada A. (2017) Adv Immunol.;133:1-36
8. Wynn TA, et al. (2013) Nature 496:445-55.
9. Valledor AF, Comalada M, Santamaría-Babi L, Lloberas J, Celada A (2010) Adv Immunol 108: 1-20
10. Xaus J, Comalada M, Valledor AF, Cardó M, Herrero C, Soler C, Lloberas J and Celada A (2001a) Immunbiology 204: 543-550.
11. Ziegler-Heitbrock L, et al., (2010) Blood 116: 74-80
12. Auffray C, et al. (2007). Science 317, 666–670.
13. Valledor AF; Lloberas J and Celada A (2015) Encyclopedia of life sciences 2015, John Wiley & Sons, Ltd: Chichester. 1-10
Macrophage, inflammation, mitochondria, genomic stability, immunosenescence, ROS, proliferation, differentiation, DNA breaks