Immune defects in caveolin-1 deficient mice

Abstract

Caveolae are mostly known as plasma membrane invaginations of 50-100 nm. However they can exist in a variety of other forms such as grape-like clusters, transcellular tubules, rosettes or pinched vesicles. Although their function appears to be complex, they have been implicated in numerous cellular processes including signal transduction, vesicular trafficking, cell cycle regulation, apoptosis, maintenece of cytoskeletal architecture.;Caveolin-1 functions as a signaling platform for many molecules involved in signal transduction. However, the expression and function of caveolin-1 in the immune system has been controversial. We have found that caveolin-1 mRNA and protein is indeed expressed in murine B-lymphocytes in a regulated manner. Caveolin-1 deficient mice displayed reduced levels of antibody in their serum. In order to examine the role of caveolin-1 in the development of immunoglobulin-mediated immune responses, we immunized wild-type and caveolin-1 deficient mice with thymus-dependent and thymus independent antigens. Results showed that caveolin-1 deficient mice have a normal response to thymus-dependent antigens, but have a reduced response to both type I and type II thymus independent antigens. However, lymphocyte populations in the spleen and peritoneum were not altered and no changes were observed in the splenic architecture. Caveolin-1 deficient B-lymphocytes did not display altered proliferation in response to different stimuli. However, we found that caveolin-1 deficient B cells have reduced IgG3 secretion in vitro in response to LPS. Together these results show convincing evidence of expression of caveolin-1 in B cells and demonstrate a role for caveolin-1 in the development of thymus-independent immune responses.;A number of studies have shown an association of pathogens with caveolae. To this date, 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 LPS. In these studies, we sought to determine the role of caveolin-1 in Salmonella pathogenesis. Cav-1-/- mice displayed a significant decrease in survival when challenged with Salmonella typhimurium . (Abstract shortened by UMI.).