title: Complement factor H in host defense and immune evasion.
abstract: Complement is the major humoral component of the innate immune system. It recognizes pathogen- and damage-associated molecular patterns, and initiates the immune response in coordination with innate and adaptive immunity. When activated, the complement system unleashes powerful cytotoxic and inflammatory mechanisms, and thus its tight control is crucial to prevent damage to host tissues and allow restoration of immune homeostasis. Factor H is the major soluble inhibitor of complement, where its binding to self markers (i.e., particular glycan structures) prevents complement activation and amplification on host surfaces. Not surprisingly, mutations and polymorphisms that affect recognition of self by factor H are associated with diseases of complement dysregulation, such as age-related macular degeneration and atypical haemolytic uremic syndrome. In addition, pathogens (i.e., non-self) and cancer cells (i.e., altered-self) can hijack factor H to evade the immune response. Here we review recent (and not so recent) literature on the structure and function of factor H, including the emerging roles of this protein in the pathophysiology of infectious diseases and cancer.
authors.affiliation: Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089, Milan, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Parente
authors.affiliation: Division of Evolution and Genomic Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Clark
authors.affiliation: Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089, Milan, Italy. Antonio.inforzato@humanitasresearch.it.|Department of Medical Biotechnologies and Translational Medicine, University of Milan, Via Vanvitelli 32, 20129, Milan, Italy. Antonio.inforzato@humanitasresearch.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Inforzato
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, M13 9PT, UK. anthony.day@manchester.ac.uk.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Day
mesh_terms: D000818:Animals; D017242:Complement Factor H / Q000737:chemistry / Q000378:metabolism*; D004194:Disease; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D011134:Polysaccharides / Q000378:metabolism; D011485:Protein Binding
chemical_list: D011134:Polysaccharides; D017242:Complement Factor H
keywords: Cancer immunology; Complement cascade; Complement factor H; Glycan markers; Inflammatory diseases; Innate immunity