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.
Highlights
Sera from mice immunized with Salmonella UF20 exhibited a high antibody titer that enhanced bacterial uptake by mouse macrophage-like RAW264.7 cells and conferred protection against S
Several studies have shown that antibodies play a crucial role in mediating immunity against Salmonella infection; these studies are limited to the use of immune sera containing polyclonal antibodies [10,13,14,16,33]
The protective efficacy of monoclonal antibody (mAb)-449 was associated with enhanced bacterial uptake by macrophages (Fig 2)
Summary
The innate and acquired immune systems are critical for controlling Salmonella infection [5,6,7,8] Both cellular and humoral factors participate in the host defense against Salmonella [9,10,11,12,13,14]; the mechanisms of bacterial clearance via specific antibodies remain obscure despite detailed evidence for antibody-mediated protection in mouse models [7,9,10,13,15]. Typhimurium with mAb-449 enhanced macrophage activation and bacterial uptake and clearance, suggesting a mechanism for antibody-mediated protection against Salmonella infection
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
