title: Oral exposure to Listeria monocytogenes in aged IL-17RKO mice: A possible murine model to study listeriosis in susceptible populations.
abstract: Foodborne Listeria monocytogenes (LM) is a cause of serious illness and death in the US. The case-fatality rate of invasive LM infection in the elderly population is >50%. The goal of this study is to establish a murine model of oral LM infection that can be used as a surrogate for human foodborne listeriosis in the geriatric population. Adult C57BL/6 (wild-type, WT) and adult or old IL17R-KO (knock-out) mice were gavaged with a murinized LM strain (Lmo-InlAm) and monitored for body-weight loss and survivability. Tissues were collected and assayed for bacterial burden, histology, and cytokine responses. When compared to WT mice, adult IL17R-KO mice are more susceptible to LM infection and showed increased LM burden and tissue pathology and a higher mortality rate. Older LM-infected KO-mice lost significantly (p < 0.02, ANOVA) more body-weight and had a higher bacterial burden in the liver (p = 0.03) and spleen as compared to adult mice. Uninfected, aged KO-mice showed a higher baseline pro-inflammatory response when compared to uninfected adult-KO mice. After infection, the pro-inflammatory cytokine, IFN-γ, mRNA in the liver was higher in the adult mice as compared to the old mice. The anti-inflammatory cytokine, IL-10, mRNA and regulatory T-cells (CD4+CD25+hor CD4+Foxp3+) cells in the aged mice increased significantly after infection as compared to adult mice. Expression of the T-cell activation marker, CD25 (IL-2Rα) in the aged mice did not increase significantly over baseline. These data suggest that aged IL17R-KO mice can be used as an in vivo model to study oral listeriosis and that aged mice are more susceptible to LM infection due to dysregulation of pro- and anti-inflammatory responses compared to adult mice, resulting in a protracted clearance of the infection.
authors: Immunobiology Branch, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration (FDA), Laurel, MD 20708, USA. Electronic address: Mohammad.alam@fda.hhs.gov.
authors: Mohammad S
authors: MS
authors: Alam
authors: Immunobiology Branch, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration (FDA), Laurel, MD 20708, USA.
authors: Matthew
authors: M
authors: Costales
authors: Immunobiology Branch, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration (FDA), Laurel, MD 20708, USA.
authors: Christopher
authors: C
authors: Cavanaugh
authors: Immunobiology Branch, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration (FDA), Laurel, MD 20708, USA.
authors: Marion
authors: M
authors: Pereira
authors: Immunobiology Branch, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration (FDA), Laurel, MD 20708, USA.
authors: Dennis
authors: D
authors: Gaines
authors: Immunobiology Branch, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration (FDA), Laurel, MD 20708, USA.
authors: Kristina
authors: K
authors: Williams
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; D000825:Animal Structures / Q000382:microbiology / Q000473:pathology; D000818:Animals; D058491:Bacterial Load; D001835:Body Weight; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D006651:Histocytochemistry; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008089:Listeria monocytogenes / Q000254:growth & development*; D008088:Listeriosis / Q000382:microbiology* / Q000473:pathology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053722:Receptors, Interleukin-17 / Q000172:deficiency*; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D016207:Cytokines; C491673:Il17ra protein, mouse; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D053722:Receptors, Interleukin-17
keywords: Aging; IL17RA-KO mice; Immune-dysregulation; Listeria monocytogenes; T helper-cells