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The Role of the IL-22 Pathway in the Lung Following Influenza Infection
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A3859 - The Role of the IL-22 Pathway in the Lung Following Influenza Infection
Author Block: K. Hebert, N. McLaughlin, D. Pociask; Department of Medicine, Tulane School of Medicine, New Orleans, LA, United States.
RATIONALE: Influenza is a viral respiratory infection that occurs in annual outbreaks and is highly contagious. While current funding strategies have focused on preventative measures such as vaccination, there has been little advancement for treatment of those hospitalized with severe viral pneumonia. Our lab focuses on the innate immune response, more specifically the IL-22 pathway, and the mechanisms involved in repair following pulmonary injury and infection. Our lab uses IL-22 as a therapeutic agent to maintain epithelial integrity and improve repair mechanisms following severe H1N1 infection.
HYPOTHESIS: IL-22 is essential for maintaining epithelial barriers following H1N1 infection.
METHODS: C57BL/6 mice were infected with 100 PFU of influenza (A/Puerto Rico/8/1934, PR8) via oropharyngeal aspiration. Treatment groups were injected intraperitoneal with human IL-22:Fc (hIL-22) three days post infection. Bronchial brushings were performed on the mice and RNA collected for analysis of upper airway cells. Evan’s Blue was injected to detect lung leak in the bronchoalveolar lavage (BAL). BAL was also collected to determine total inflammatory and differential leukocyte cell counts. One half of the lung was collected for RNA analysis and the other half was formalin fixed for IHC. Primary and cultured airway cells (BEAS-2B and NHBE) were also infected with PR8 and treated with hIL-22. Cells were then collected for RNA analysis or used for immunofluorescence (IF). All samples were analyzed for induction of IL-22 receptor alpha 1 (IL-22Rα1) and recovery of tight junctions following infection. IL-22Rα1 induction specificity following infection was confirmed via Poly I:C, a TLR3 agonist, and STAT inhibitors.
RESULTS: IL-22Rα1 induction following infection was determined to be TLR3, Interferon β and STAT1 dependent. Treatment with IL-22 after infection recovered tight junctions both in vitro and in vivo as confirmed by qPCR and IF. Treatment also led to significantly less lung damage and weight loss when compared to infected controls in vivo. Viral clearance and burden were not affected by treatment.
CONCLUSIONS: These results suggest that after IL-22Rα1 is induced, recombinant IL-22 can be used therapeutically to maintain epithelial integrity and mitigate damage following severe influenza infection.
Author Block: K. Hebert, N. McLaughlin, D. Pociask; Department of Medicine, Tulane School of Medicine, New Orleans, LA, United States.
RATIONALE: Influenza is a viral respiratory infection that occurs in annual outbreaks and is highly contagious. While current funding strategies have focused on preventative measures such as vaccination, there has been little advancement for treatment of those hospitalized with severe viral pneumonia. Our lab focuses on the innate immune response, more specifically the IL-22 pathway, and the mechanisms involved in repair following pulmonary injury and infection. Our lab uses IL-22 as a therapeutic agent to maintain epithelial integrity and improve repair mechanisms following severe H1N1 infection.
HYPOTHESIS: IL-22 is essential for maintaining epithelial barriers following H1N1 infection.
METHODS: C57BL/6 mice were infected with 100 PFU of influenza (A/Puerto Rico/8/1934, PR8) via oropharyngeal aspiration. Treatment groups were injected intraperitoneal with human IL-22:Fc (hIL-22) three days post infection. Bronchial brushings were performed on the mice and RNA collected for analysis of upper airway cells. Evan’s Blue was injected to detect lung leak in the bronchoalveolar lavage (BAL). BAL was also collected to determine total inflammatory and differential leukocyte cell counts. One half of the lung was collected for RNA analysis and the other half was formalin fixed for IHC. Primary and cultured airway cells (BEAS-2B and NHBE) were also infected with PR8 and treated with hIL-22. Cells were then collected for RNA analysis or used for immunofluorescence (IF). All samples were analyzed for induction of IL-22 receptor alpha 1 (IL-22Rα1) and recovery of tight junctions following infection. IL-22Rα1 induction specificity following infection was confirmed via Poly I:C, a TLR3 agonist, and STAT inhibitors.
RESULTS: IL-22Rα1 induction following infection was determined to be TLR3, Interferon β and STAT1 dependent. Treatment with IL-22 after infection recovered tight junctions both in vitro and in vivo as confirmed by qPCR and IF. Treatment also led to significantly less lung damage and weight loss when compared to infected controls in vivo. Viral clearance and burden were not affected by treatment.
CONCLUSIONS: These results suggest that after IL-22Rα1 is induced, recombinant IL-22 can be used therapeutically to maintain epithelial integrity and mitigate damage following severe influenza infection.
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