title: Specific Monoclonal Antibody Overcomes the Salmonella enterica Serovar Typhimurium's Adaptive Mechanisms of Intramacrophage Survival and Replication.
abstract: Salmonella-specific antibodies play an important role in host immunity; however, the mechanisms of Salmonella clearance by pathogen-specific antibodies remain to be completely elucidated since previous studies on antibody-mediated protection have yielded inconsistent results. These inconsistencies are at least partially attributable to the use of polyclonal antibodies against Salmonella antigens. Here, we developed a new monoclonal antibody (mAb)-449 and identified its related immunogen that protected BALB/c mice from infection with Salmonella enterica serovar Typhimurium. In addition, these data indicate that the mAb-449 immunogen is likely a major protective antigen. Using in vitro infection studies, we also analyzed the mechanism by which mAb-449 conferred host protection. Notably, macrophages infected with mAb-449-treated S. Typhimurium showed enhanced pathogen uptake compared to counterparts infected with control IgG-treated bacteria. Moreover, these macrophages produced elevated levels of pro-inflammatory cytokine TNFα and nitric oxide, indicating that mAb-449 enhanced macrophage activation. Finally, the number of intracellular bacteria in mAb-449-activated macrophages decreased considerably, while the opposite was found in IgG-treated controls. Based on these findings, we suggest that, although S. Typhimurium has the potential to survive and replicate within macrophages, host production of a specific antibody can effectively mediate macrophage activation for clearance of intracellular bacteria.
authors.affiliation: National Institute of Animal Health, NARO, 3-1-5 Kannondai, Tsukuba, Ibaraki, 305-0856, Japan.
authors.forename: Swarmistha Devi
authors.initials: SD
authors.lastname: Aribam
authors.affiliation: National Institute of Animal Health, NARO, 3-1-5 Kannondai, Tsukuba, Ibaraki, 305-0856, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Harada
authors.affiliation: National Institute of Animal Health, NARO, 3-1-5 Kannondai, Tsukuba, Ibaraki, 305-0856, Japan.
authors.forename: Marta
authors.initials: M
authors.lastname: Elsheimer-Matulova
authors.affiliation: National Institute of Animal Health, NARO, 3-1-5 Kannondai, Tsukuba, Ibaraki, 305-0856, Japan.
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Iwata
authors.affiliation: National Institute of Animal Health, NARO, 3-1-5 Kannondai, Tsukuba, Ibaraki, 305-0856, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Kanehira
authors.affiliation: National Institute of Animal Health, NARO, 3-1-5 Kannondai, Tsukuba, Ibaraki, 305-0856, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hikono
authors.affiliation: Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Matsui
authors.affiliation: National Institute of Animal Health, NARO, 3-1-5 Kannondai, Tsukuba, Ibaraki, 305-0856, Japan.
authors.forename: Yohsuke
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: National Institute of Animal Health, NARO, 3-1-5 Kannondai, Tsukuba, Ibaraki, 305-0856, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Shimoji
authors.affiliation: National Institute of Animal Health, NARO, 3-1-5 Kannondai, Tsukuba, Ibaraki, 305-0856, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Eguchi
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D002470:Cell Survival; D004261:DNA Replication; D007109:Immunity / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012481:Salmonella Infections, Animal / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology*; D065288:Serogroup
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal