Caveolin-1-deficient mice show defects in innate immunity and inflammatory immune response during Salmonella enterica serovar Typhimurium infection.

Abstract

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.

• Authors: Freddy A Medina, Cecilia J de Almeida, Elliott Dew, Jiangwei Li, Gloria Bonuccelli, Terence M Williams, Alex W Cohen, Richard G Pestell, Philippe G Frank, Herbert B Tanowitz, Michael P Lisanti
• Journal: Infection and immunity (Infect Immun) Vol. 74 Issue 12 Pg. 6665-74 (Dec 2006) ISSN: 0019-9567 [Print] United States
• PMID: 16982844 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Caveolin 1
• Cytokines
• Lipopolysaccharides
• STAT3 Transcription Factor
• Stat3 protein, mouse
• Nitric Oxide

Topics

• Animals
• Caveolin 1 (deficiency, genetics, physiology)
• Cytokines (genetics, metabolism)
• Granuloma (immunology, microbiology, pathology)
• Immunity, Innate (genetics)
• Lipopolysaccharides (immunology)
• Liver (immunology, pathology)
• Macrophages (immunology, microbiology)
• Mice
• Mice, Knockout
• Neutrophils (immunology)
• Nitric Oxide (metabolism)
• STAT3 Transcription Factor (metabolism)
• Salmonella Infections (genetics, immunology, pathology)
• Salmonella typhimurium
• Spleen (immunology, pathology)