Caveolin-1-Deficient Mice Show Defects in Innate Immunity and Inflammatory Immune Response during Salmonella enterica Serovar Typhimurium Infection
| Autor: | Terence M. Williams, Cecilia J. de Almeida, Philippe G. Frank, Richard G. Pestell, Alex W. Cohen, Herbert B. Tanowitz, Jiangwei Li, Michael P. Lisanti, Freddy A. Medina, Elliott Dew, Gloria Bonuccelli |
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| Rok vydání: | 2006 |
| Předmět: |
Lipopolysaccharides
STAT3 Transcription Factor Salmonella typhimurium Chemokine Salmonella Lipopolysaccharide Neutrophils Caveolin 1 Immunology Inflammation Nitric Oxide medicine.disease_cause Microbiology Proinflammatory cytokine Mice chemistry.chemical_compound Immune system medicine Animals Mice Knockout Host Response and Inflammation Granuloma Innate immune system biology Macrophages biology.organism_classification Immunity Innate Infectious Diseases Liver chemistry Salmonella enterica Salmonella Infections cardiovascular system biology.protein Cytokines Parasitology medicine.symptom Spleen |
| Zdroj: | Infection and Immunity. 74:6665-6674 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | A number of studies have shown an association of pathogens with caveolae. To this date, however, there are no studies showing a role for caveolin-1 in modulating immune responses against pathogens. Interestingly, expression of caveolin-1 has been shown to occur in a regulated manner in immune cells in response to lipopolysaccharide (LPS). Here, we sought to determine the role of caveolin-1 (Cav-1) expression in Salmonella pathogenesis. Cav-1 −/− mice displayed a significant decrease in survival when challenged with Salmonella enterica serovar Typhimurium. Spleen and tissue burdens were significantly higher in Cav-1 −/− mice. However, infection of Cav-1 −/− macrophages with serovar Typhimurium did not result in differences in bacterial invasion. In addition, Cav-1 −/− mice displayed increased production of inflammatory cytokines, chemokines, and nitric oxide. Regardless of this, Cav-1 −/− mice were unable to control the systemic infection of Salmonella . The increased chemokine production in Cav-1 −/− mice resulted in greater infiltration of neutrophils into granulomas but did not alter the number of granulomas present. This was accompanied by increased necrosis in the liver. However, Cav-1 −/− macrophages displayed increased inflammatory responses and increased nitric oxide production in vitro in response to Salmonella LPS. These results show that caveolin-1 plays a key role in regulating anti-inflammatory responses in macrophages. Taken together, these data suggest that the increased production of toxic mediators from macrophages lacking caveolin-1 is likely to be responsible for the marked susceptibility of caveolin-1-deficient mice to S. enterica serovar Typhimurium. |
| Databáze: | OpenAIRE |
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