Specific Monoclonal Antibody Overcomes the Salmonella enterica Serovar Typhimurium's Adaptive Mechanisms of Intramacrophage Survival and Replication

• Published in: PloS one Vol. 11; no. 3; p. e0151352
• Main Authors: Aribam, Swarmistha Devi, Harada, Tomoyuki, Elsheimer-Matulova, Marta, Iwata, Taketoshi, Kanehira, Katsushi, Hikono, Hirokazu, Matsui, Hidenori, Ogawa, Yohsuke, Shimoji, Yoshihiro, Eguchi, Masahiro
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.03.2016; Public Library of Science (PLoS)
• Subjects: Animals; Antibodies, Bacterial; Antibodies, Monoclonal; Antigens; Bacteria; Biology and Life Sciences; Cell activation; Cell Survival; Complications and side effects; DNA Replication; Dosage and administration; Drug therapy; Ethics; Experiments; Health aspects; Immunity; Immunity - immunology; Immunoglobulin G; Infections; Inflammation; Intracellular; Macrophages; Macrophages - immunology; Macrophages - microbiology; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Monoclonal antibodies; Nitric oxide; Pathogens; Physiological aspects; Polyclonal antibodies; Protective antigen; Salmonella; Salmonella enterica; Salmonella Infections, Animal - immunology; Salmonella typhimurium - immunology; Salmonellosis; Serogroup; Studies; Survival; Tumor necrosis factor-α; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0151352

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.