title: Human L-ficolin, a recognition molecule of the lectin activation pathway of complement, activates complement by binding to pneumolysin, the major toxin of Streptococcus pneumoniae.
abstract: The complement system is an essential component of the immune response, providing a critical line of defense against different pathogens including S. pneumoniae. Complement is activated via three distinct pathways: the classical (CP), the alternative (AP) and the lectin pathway (LP). The role of Pneumolysin (PLY), a bacterial toxin released by S. pneumoniae, in triggering complement activation has been studied in vitro. Our results demonstrate that in both human and mouse sera complement was activated via the CP, initiated by direct binding of even non-specific IgM and IgG3 to PLY. Absence of CP activity in C1q(-/-) mouse serum completely abolished any C3 deposition. However, C1q depleted human serum strongly opsonized PLY through abundant deposition of C3 activation products, indicating that the LP may have a vital role in activating the human complement system on PLY. We identified that human L-ficolin is the critical LP recognition molecule that drives LP activation on PLY, while all of the murine LP recognition components fail to bind and activate complement on PLY. This work elucidates the detailed interactions between PLY and complement and shows for the first time a specific role of the LP in PLY-mediated complement activation in human serum.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom ; Department of Microbiology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: Youssif M
authors.initials: YM
authors.lastname: Ali
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom ; Department of Microbiology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: Hany I
authors.initials: HI
authors.lastname: Kenawy
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Adnan
authors.initials: A
authors.lastname: Muhammad
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Sim
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrew
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Wilhelm J
authors.initials: WJ
authors.lastname: Schwaeble
mesh_terms: D000328:Adult; D001426:Bacterial Proteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D003167:Complement Activation / Q000276:immunology*; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism; D003176:Complement C3 / Q000276:immunology / Q000378:metabolism; D037582:Complement Pathway, Mannose-Binding Lectin; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D013301:Streptolysins / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism*; D000097604:Ficolins
chemical_list: D001426:Bacterial Proteins; D015922:Complement C1q; D003176:Complement C3; D003165:Complement System Proteins; D037102:Lectins; D011994:Recombinant Proteins; D013301:Streptolysins; D000097604:Ficolins; C032290:plY protein, Streptococcus pneumoniae