Generation of protection against Francisella novicida in mice depends on the pathogenicity protein PdpA,but not PdpC or PdpD |
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| Affiliation: | 1. Laboratory of Mycobacterial Diseases and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, 1401 Rockville Pike, HFM-431, Rockville, MD 20852, USA;2. Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada;1. Istanbul University, Cerrahpasa Faculty of Medicine, Department of Nuclear Medicine, Istanbul, Turkey;2. Istanbul Bağcılar Training and Education Hospital, Department of Nuclear Medicine, Istanbul, Turkey;3. Yıldırım Beyazıt University Hospital, Department of Nuclear Medicine, Ankara, Turkey;1. Division of Neurology, Department of Medicine, University of Toronto, 1 King''s College Cir, Toronto, ON M5S 1A8, Canada;2. Department of Genetics and Development, Toronto Western Research Institute, 399 Bathurst St, McL 12-407 Toronto, ON M5T 2S8, Canada;3. Lyndhurst Centre, Toronto Rehabilitation Institute, 520 Sutherland Dr, Toronto, ON M4G 3V9, Canada;4. Division of Neurosurgery, Department of Surgery, University of Toronto, 1 King''s College Cir, Toronto, ON M5S 1A8, Canada;5. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave, Suite 600, Toronto, ON M5G 1X5, Canada;6. Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King''s College Cir, Toronto, ON M5S 1A8, Canada;7. Division of Neuropathology, Department of Laboratory Medicine and Pathobiology, Toronto General Hospital, University Health Network, 200 Elizabeth St, Eaton South Wing, 11th Floor, Toronto, ON M5G 2C4, Canada;1. Nano Electrochemistry Lab (NEL), Department of Chemistry, National Institute of Technology Puducherry, Karaikal 609-609, India;2. Department of Electronics and Communications Engineering, National Institute of Technology Puducherry, Karaikal 609-609, India;3. Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia;4. Department of Medicinal and Applied Chemistry, and Research Centre for Environmental Medicine, Kaohsiung Medical University (KMU), Kaohsiung City 807, Taiwan;5. Department of Medical Research, Kaohsiung Medical University Hospital (KMUH), Kaohsiung City 807, Taiwan;6. Department of Chemistry, National Sun Yat-sen University (NSYSU), Kaohsiung City 804, Taiwan |
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| Abstract: | Previous results suggest that mutations in most genes in the Francisella pathogenicity island (FPI) attenuate the bacterium. Using a mouse model, here we determined the impact of mutations in pdpA, pdpC, and pdpD in Francisella novicida on in vitro replication in macrophages, and in vivo immunogenicity. In contrast to most FPI genes, deletion of pdpC (FnΔpdpC) and pdpD (FnΔpdpD) from F. novicida did not impact growth in mouse bone-marrow derived macrophages. Nonetheless, both FnΔpdpC and FnΔpdpD were highly attenuated when administered intradermally. Infected mice produced relatively normal anti-F. novicida serum antibodies. Further, splenocytes from infected mice controlled intramacrophage Francisella replication, indicating T cell priming, and mice immunized by infection with FnΔpdpC or FnΔpdpD survived secondary lethal parenteral challenge with either F. novicida or Francisella tularensis LVS. In contrast, deletion of pdpA (FnΔpdpA) ablated growth in macrophages in vitro. FnΔpdpA disseminated and replicated poorly in infected mice, accompanied by development of some anti-F. novicida serum antibodies. However, primed Th1 cells were not detected, and vaccinated mice did not survive even low dose challenge with either F. novicida or LVS. Taken together, these results suggest that successful priming of Th1 cells, and protection against lethal challenge, depends on expression of PdpA. |
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| Keywords: | Pathogenicity island T lymphocytes Protective immunity Mice |
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