title: Human IgG isotypes and activating Fcγ receptors in the interaction of Salmonella enterica serovar Typhimurium with phagocytic cells.
abstract: Several classes and multiple subclasses of immunoglobulins are produced towards protein and polysaccharide antigens in response to Salmonella infection and play a key role in protection against systemic disease. The targeting of Salmonella to Fc receptors (FcR) on phagocytes is a key step in the antibody-mediated antibacterial functions of host cells. We wished to compare the relative efficiency of different human IgG subclasses, which targeted the Salmonella enterica OmpA surface protein in modulating the interaction of bacteria with human phagocytes. To this end, we developed a novel system by tagging OmpA with a foreign CD52 mimotope (TSSPSAD) and opsonizing the bacteria with a panel of humanized CD52 antibodies that share the same antigen-binding V-region, but have constant regions of different subclasses. Our data revealed that opsonization with all the IgG subclasses increases Salmonella uptake by human phagocytes. IgG3 resulted in the highest level of bacterial uptake and the highest average bacterial load per infected cell, which was closely followed by IgG1, then IgG4 and lastly IgG2. Phagocytosis mediated by IgG1, IgG3 and IgG4 had a higher dependency on FcγRI than FcγRIIA, whereas IgG2-mediated phagocytosis required FcγRIIA more than FcγRI. The results show that IgG binding to OmpA increases the uptake of Salmonella by human phagocytic cells and that the efficiency of this process depends both on the subclass of the IgG and the type of FcR that is available for antibody binding.
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Yun S
authors.initials: YS
authors.lastname: Goh
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Grant
authors.forename: Olivier
authors.initials: O
authors.lastname: Restif
authors.forename: Trevelyan J
authors.initials: TJ
authors.lastname: McKinley
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Armour
authors.forename: Michael R
authors.initials: MR
authors.lastname: Clark
authors.forename: Pietro
authors.initials: P
authors.lastname: Mastroeni
mesh_terms: D005455:Fluorescent Antibody Technique; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000276:immunology*; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D010586:Phagocytes; D017452:Receptors, IgG / Q000276:immunology*; D012480:Salmonella Infections / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D017452:Receptors, IgG