Granuloma Immunology, Pathology
Dov L. Boros,
Wayne State University School of Medicine, USA
Nicholas W. Lukacs,
University of Michigan, USA
Stephen W. Chensue,
University of Michigan, USA
The prototype of the granulomatous inflammation,-the mycobacterial tubercle,was first described by pathologists over 150 years ago.Granulomas are focal, chronic tissue inflammations in reaction to persistent microbial invaders,as well as chemical irritants.Immune granulomas are generated by CD4+T effector/helper cells.This Research Topic is initiated to provide a specific state-of-the-art forum dedicated only to the various aspects of the granulomatous response.This includes the molecular basis of the initial interaction of the innate and adaptive immune responses:TLR,NRL and other innate receptors,the assembly and regulation of inflammasomes and inflammatory cytokine production.The fate of the mature granuloma is decided by the intensity and duration of the antigenic stimuli,and the action of the Th1,Th2 and Treg lymphocytes recruited to the site.The complexity of the ever expanding cytokine/chemokine web that sustains or regulates the inflammation and mediates the antimicrobial effect poses a major challenge for researchers to unravel and to elucidate.No less a challenge are the cytokine-activated macrophages, that play a major role in the elimination of the persistent pathogen.While doing this,macrophages release reactive oxygen and nitrogen free-radicals that cause tissue damage.Thus,yet another important task is the separation of the protective from the destructive effect of the inflammatory response.Macrophages comprise the bulk of the granulomas.Recent research shows that they are a heterogeneous population and can be divided into more or less two distinct subpopulations.Thus,analysis of the function of M1- or M2-type macrophages with antimicrobial action-or others that activate fibroblasts for collagen deposition or conversely,control extracellular matrix turnover and fibrous healing of the inflammation is of much current research interest.Sarcoidosis,Crohn’s disease and primary biliary cirrhosis comprise a distinct group of granulomatous diseases where controversy about the etiologic agent(s) and host responses still exists.Whereas in sarcoidosis and Crohn’s disease microbial triggers have been proposed,in primary biliary cirrhosis the granulomagenic agent is still unknown.The progressive,often sever pathology affects single(intestines,liver) organs,thus little or no protective role can be assigned to the chronic granulomatous inflammations.In genetically predisposed individuals chronicity is believed to be sustained by the innate,adaptive,and autoimmune responses.Contributions to this Research Topic will promote knowledge on this complex protective vs/destructive response,and can lead to its improved handling in clinical practice.