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T4-04 Assessing Immunological Risk of Listeria Infection in the Aging Population Using a Susceptible Animal Model

Sunday, July 26, 2015: 2:15 PM
C124 (Oregon Convention Center)
Mohammad Samiul Alam , U.S. Food and Drug Administration-CFSAN , Laurel , MD
Matthew Costales , CFSAN/U.S. Food and Drug Administration , Laurel , MD
Christopher Cavanagh , U.S. Food and Drug Administration-CFSAN , Laurel , MD
Dennis Gaines , U.S. Food and Drug Administration-CFSAN , Laurel , MD
Marion Pereira , FDA , Laurel , MD
Kristina Williams , U.S. Food and Drug Administration-CFSAN , Laurel , MD
Audio File Recorded Presentation
Introduction: Foodborne Listeria monocytogenes (LM) is a cause of serious illness and death in the United States. The case-fatality rate of invasive LM infection in the elderly population is >50%.

Purpose: 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 aged population.

Methods: C57BL/6 (wild-type, WT) and IL17R-KO (Knock-Out) mice were orally infected with increasing doses of 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 response. Isolated splenocytes were assayed for cytokine mRNA response (IL-2R, TNF-α, IL-10 and IFN-γ) and protein by flow cytometry.

Results: When compared to WT mice, IL17R-KO mice are more susceptible to LM infection and showed increased tissue pathology, LM burden and a higher mortality rate. Old LM-infected KO-mice lost significantly (P = 0.001, ANOVA) more body-weight and had a higher bacterial burden in liver (P = 0.03) and spleen (P = 0.05) as compared to young mice. Uninfected, old KO-mice showed a higher baseline pro-inflammatory response when compared to young, uninfected mice. After infection, the pro-inflammatory cytokine (IFN-g and TNF-a) mRNA and protein in the liver or spleen were higher in the young mice compared to the old mice. Anti-inflammatory cytokine (e.g., IL-10), Treg (CD4+CD25+) cells, and T-cell activation marker, CD25 (IL-2Ra) expression in the old mice did not increase over baseline, suggesting cellular anergy and immunosenescence in the old mice.

Significance: These data suggest that IL17R-KO mice can be used as in vivo model to study oral Listeriosis. We further showed that older mice are more susceptible to LM infection due to slower and reduced pro-inflammatory response compared to young mice, resulting in a delayed clearance of the infection.

Back to: Technical Session 4 – General Microbiology
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