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A5480 - Chitotriosidase Protects Mice Against Influenza Lung Infection
Author Block: L. Sharma1, A. K. Amick1, A. J. Losier1, V. A. Brady1, S. Gautam1, W. Liu1, S. Lee2, C. Lee3, J. A. Elias4, C. Dela Cruz1; 1Pulmonary, Critical Care and Sleep Medicine, Yale University, New Haven, CT, United States, 2Pulmonology and Critical Care Medicine, Asan Medical Center, Seoul, Korea, Republic of, 3MMI, Brown University, Providence, RI, United States, 4Warren Alpert Medical School, Brown University, Providence, RI, United States.
Lung infection with influenza are one of the leading cause of pneumonia in healthy people. In spite of continuous vaccination efforts, 5-15 % of the population suffer from influenza infection annually.
While most infections are moderate, it can cause severe infections in elderly people or those with comorbidities. Approximately half million deaths annually result from influenza, around the world. Preventive and therapeutic options are limited due to emergence of new variants of influenza strains. Better understanding of host antiviral mechanisms against influenza can provide new therapeutic options.
Chitotriosidase (Chit1) belongs to the family of 18-glycosyl hydrolases and is the most prominent chitinase present in humans. In absence of chitin synthesis in mammals, chitinases have been proposed to play important roles in host immunity. However, such a role for Chit1 has not been proven experimentally.
In this study, we explored the role of Chit1 in a mouse model of influenza lung infection using mice that are deficient in Chit1 (Chit1 -/-). Mice were infected intra-nasally with PR8 strain of influenza and observed for clinical signs of disease severity. Mice were sacrificed at different time points to understand the underlying mechanisms. Our data show that in the absence of Chit1, mice fail to recover normally with a significantly lower weight gain in the recovery phase of influenza infection (day 9-16). The slow recovery is marked by significantly elevated inflammation at day 16. The increased inflammation is mainly due to elevated lymphocytes in Chit1-/- mice, as similar number of macrophages and neutrophils were observed among two groups at day 16. At this time point, an increase in collagen content in the lung was observed, suggesting elevated fibrotic changes in the lung of Chit1 -/- mice. Similar observations were made in lung pathology where increased trichrome staining was observed.
To understand the underlying mechanisms, we investigated inflammatory response at early time points of inflammation. While there was no difference in total WBC counts, macrophages, neutrophils and CD4+ cells in the BAL at day 3 and day 7, our data indicate an impairment in the recruitment of CD8 positive T cells in the airways of Chit1-/- mice at day 7 post infection. These data suggest possible role of Chit1 in generating antiviral immunity through CD8 T cells and recovery phase of influenza infections.
Further mechanisms are being elucidated. These data suggest an important role of Chit1 during viral lung infection.