Increased Susceptibility of Diabetic Mice to Influenza Virus Infection: Compromise of Collectin-Mediated Host Defense of the Lung by Glucose?
- Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3052,1 and
- The Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, Victoria 3052,2 Australia, and
- Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 631103
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Fig. 1.Replication of influenza A viruses in the lungs of diabetic and nondiabetic mice. (A) Virus titers in the lungs of individual diabetic mice (•) and nondiabetic littermates (○) at various times after i.n. inoculation with 105 PFU of A/Phil/82 virus. The dashed line represents the lower limit of detection of virus in lung homogenates. At all time points except 4 h postinfection, virus titers for diabetic mice were significantly higher than those for nondiabetic mice (P< 0.01, Student’s t test). (B and C) Virus titers in the lungs of diabetic (▪) and nondiabetic (□) mice 3 days after i.n. inoculation with different doses of A/HKx31 (B) or A/PR/8/34 (C) influenza virus. Data are the mean lung virus titers (± 1 standard error) for groups of 3 mice. Asterisks indicate lung virus titers of diabetic mice that were significantly different from those of the corresponding nondiabetic controls. ∗, P < 0.02; ∗∗, P < 0.01, Student’s t test.
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Fig. 2.Relationship between blood glucose levels and the ability of influenza virus to replicate in the lungs of mice. (A) Blood glucose levels of male (▪ and □) and female (• and ○) mice were determined 4 h before i.n. infection with 105 PFU of A/Phil/82, and virus titers in the lungs were determined at 3 days postinfection. Diabetic animals are indicated by closed symbols, and nondiabetic animals are indicated by open symbols. (B) Effect of insulin treatment on replication of influenza virus in the lungs of diabetic mice. Data are the lung virus titers for individual diabetic mice (•), diabetic mice given subcutaneous injections of insulin every 6 h (⊕), and nondiabetic controls (○) 24 h after i.n. infection with 105 PFU of A/Phil/82 virus. The dashed line represents the lower limit of detection of virus in lung homogenates.
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Fig. 3.Effect of glucose on neutralization of influenza virus by SP-D. A/Phil/82 virus was incubated with (•) or without (○) recombinant rat SP-D (final concentration, 2 μg/ml) in the absence or presence of increasing concentrations of glucose (5 to 25 mM) for 60 min at 37°C, and the residual infectivity of the samples was determined by fluorescent focus assay on MDCK cell monolayers.
- Copyright © 1998 American Society for Microbiology
