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New murine model of bronchopneumonia due to cell-bound Haemophilus influenzae
S Miyazaki1, T Nunoya, T Matsumoto
1Department of Microbiology, School of Medicine, Toho University, Tokyo, Japan.
Abstract:
This murine model of nontypeable (unencapsulated) Haemophilus influenzae (NTHI) bronchopneumonia used organisms bound to mouse fetal lung (MFL) cells as an inoculum. Pretreatment of the mice with 40 microL of 1% formalin 3 days before intranasal instillation of the bacteria was necessary to allow infection. The number of NTHI recovered from the lungs plus trachea on day 7 after instillation was >100 times the number originally inoculated. Later, however, the number of recovered bacteria diminished gradually, and by day 14 it was almost identical to the original inoculum size. Serum IgM also peaked on day 7 after infection, after which IgG increased while IgM decreased. Histologically, bronchoalveolar infiltration of neutrophils was observed on day 3 after inoculation and continued at least for the following 4 days. The present experiment demonstrates that MFL cells can protect bacteria that have invaded the cells from the opsonizing and killing activities of host humoral defense mechanisms.
Insights
This study developed a mouse model for nontypeable Haemophilus influenzae (NTHI) bronchopneumonia. Mouse fetal lung cells protect NTHI from immune responses, aiding infection establishment.
Area of Science:
- * Microbiology
- * Immunology
- * Pulmonary Medicine
Background:
- * Nontypeable Haemophilus influenzae (NTHI) is a significant cause of respiratory infections.
- * Understanding NTHI pathogenesis and host-pathogen interactions is crucial for developing effective treatments.
Purpose of the Study:
- * To establish a murine model for NTHI bronchopneumonia using NTHI bound to mouse fetal lung (MFL) cells.
- * To investigate the dynamics of NTHI infection and the host immune response in this model.
- * To determine the role of MFL cells in protecting NTHI from host defense mechanisms.
Main Methods:
- * Intranasal instillation of NTHI bound to MFL cells into pretreated mice.
- * Quantification of bacterial load in lungs and trachea over 14 days.
- * Measurement of serum IgM and IgG antibody levels.
- * Histological examination of lung tissue for inflammatory cell infiltration.
Main Results:
- * A formalin pretreatment was necessary for successful NTHI infection.
- * Bacterial load peaked at day 7 post-infection (>100x inoculum) and decreased by day 14.
- * Serum IgM peaked on day 7, followed by an increase in IgG.
- * Neutrophil infiltration was observed in bronchoalveolar spaces from day 3 onwards.
- * MFL cells protected intracellular NTHI from humoral immune mechanisms.
Conclusions:
- * The developed murine model effectively replicates NTHI bronchopneumonia.
- * MFL cells play a critical role in NTHI survival by evading host immune responses.
- * This model provides insights into NTHI pathogenesis and potential therapeutic targets.