title: Old dogs-new tricks: immunoregulatory properties of C3 and C5 cleavage fragments.
abstract: The activation of the complement system by canonical and non-canonical mechanisms results in the generation of multiple C3 and C5 cleavage fragments including anaphylatoxins C3a and C5a as well as opsonizing C3b/iC3b. It is now well appreciated that anaphylatoxins not only act as pro-inflammatory mediators but as immunoregulatory molecules that control the activation status of cells and tissue at several levels. Likewise, C3b/iC3b is more than the opsonizing fragment that facilitates engulfment and destruction of targets by phagocytes. In the circulation, it also facilitates the transport and delivery of bacteria and immune complexes to phagocytes, through a process known as immune adherence, with consequences for adaptive immunity. Here, we will discuss non-classical immunoregulatory properties of C3 and C5 cleavage fragments. We highlight the influence of anaphylatoxins on Th2 and Th17 cell development during allergic asthma with a particular emphasis on their role in the modulation of CD11b+conventional dendritic cells and monocyte-derived dendritic cells. Furthermore, we discuss the control of anaphylatoxin-mediated activation of dendritic cells and allergic effector cells by adaptive immune mechanisms that involve allergen-specific IgG1 antibodies and plasma or regulatory T cell-derived IL-10 production. Finally, we take a fresh look at immune adherence with a particular focus on the development of antibacterial cytotoxic T-cell responses.
authors: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany. admar.verschoor@uksh.de.
authors: Admar
authors: A
authors: Verschoor
authors: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
authors: Christian M
authors: CM
authors: Karsten
authors: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
authors: Steven P
authors: SP
authors: Broadley
authors: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
authors: Yves
authors: Y
authors: Laumonnier
authors: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany. joerg.koehl@uksh.de.|Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. joerg.koehl@uksh.de.
authors: Jörg
authors: J
authors: Köhl
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D002454:Cell Differentiation; D003167:Complement Activation; D003176:Complement C3 / Q000276:immunology / Q000378:metabolism*; D003182:Complement C5 / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007113:Immunity, Innate; D056747:Immunomodulation; D059748:Proteolysis; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D003176:Complement C3; D003182:Complement C5
keywords: Fc receptors; asthma; complement; infectious diseases; inflammation; lung