title: IL-23 p19 knockout mice exhibit minimal defects in responses to primary and secondary infection with Francisella tularensis LVS.
abstract: Our laboratory's investigations into mechanisms of protective immunity against Francisella tularensis Live Vaccine Strain (LVS) have uncovered mediators important in host defense against primary infection, as well as those correlated with successful vaccination. One such potential correlate was IL-12p40, a pleiotropic cytokine that promotes Th1 T cell function as part of IL-12p70. LVS-infected IL-12p40 deficient knockout (KO) mice maintain a chronic infection, but IL-12p35 KO mice clear LVS infection; thus the role that IL-12p40 plays in immunity to LVS is independent of the IL-12p70 heterodimer. IL-12p40 can also partner with IL-23p19 to create the heterodimeric cytokine IL-23. Here, we directly tested the role of IL-23 in LVS resistance, and found IL-23 to be largely dispensable for immunity to LVS following intradermal or intranasal infection. IL-23p19 KO splenocytes were fully competent in controlling intramacrophage LVS replication in an in vitro overlay assay. Further, antibody responses in IL-23p19 KO mice were similar to those of normal wild type mice after LVS infection. IL-23p19 KO mice or normal wild type mice that survived primary LVS infection survived maximal doses of LVS secondary challenge. Thus p40 has a novel role in clearance of LVS infection that is unrelated to either IL-12 or IL-23.
authors.affiliation: 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, Rockville, Maryland, United States of America.
authors.forename: Sherry L
authors.initials: SL
authors.lastname: Kurtz
authors.affiliation: 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, Rockville, Maryland, United States of America.
authors.forename: Alicia Y
authors.initials: AY
authors.lastname: Chou
authors.affiliation: 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, Rockville, Maryland, United States of America.
authors.forename: Klara
authors.initials: K
authors.lastname: Kubelkova
authors.affiliation: Pathway Biology, Merck Research Laboratories, Palo Alto, CA, United States of America.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cua
authors.affiliation: 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, Rockville, Maryland, United States of America.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Elkins
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines; D060085:Coinfection / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005604:Francisella tularensis / Q000276:immunology / Q000502:physiology*; D053760:Interleukin-23 Subunit p19 / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014406:Tularemia / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014613:Vaccines, Attenuated
chemical_list: D001428:Bacterial Vaccines; D053760:Interleukin-23 Subunit p19; D014613:Vaccines, Attenuated