title: Macrophage responses to bacterial toxins: a balance between activation and suppression.
abstract: Toxins secreted by bacteria can impact the host in a number of different ways. In some infections, toxins play a crucial and central role in pathogenesis (i.e., anthrax), while in other bacterial infections, the role of toxins is less understood. The cholesterol-dependent cytolysins (CDCs), of which streptolysin O is a prototype, are a class of pore-forming toxins produced by many gram-positive bacteria and have only been studied in a few experimental infection models. Our laboratory has demonstrated that CDCs have effects on macrophages that are both pro- and anti-inflammatory. Here, we review evidence that CDCs promote inflammation by driving secretion of IL-1β and HMGB-1 from macrophages in a NLRP3-dependent manner, while also causing shedding of membrane microvesicles from cells that can interact with macrophages and inhibit TNF-α release. CDCs thus impact macrophage function in ways that may be both beneficial and detrimental to the host.
authors: Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors: Peter A
authors: PA
authors: Keyel
authors: Michelle E
authors: ME
authors: Heid
authors: Russell D
authors: RD
authors: Salter
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism* / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism; D003603:Cytotoxins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D052899:Pore Forming Cytotoxic Proteins / Q000378:metabolism; D013744:Tetanus Toxin / Q000378:metabolism / Q000494:pharmacology
chemical_list: D001427:Bacterial Toxins; D003603:Cytotoxins; D052899:Pore Forming Cytotoxic Proteins; D013744:Tetanus Toxin; C026167:tetanolysin; D002784:Cholesterol