|MCCRAY, JR., PAUL|
Submitted to: American Society for Microbiology Annual Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 5/20/2001
Publication Date: N/A
Technical Abstract: Host defense relies on the concerted action of antigen non-specific innate immunity and antigen specific adaptive immunity. Recently, alpha defensins have been reported to induce an adaptive immune response to ovalbumin (OVA) in mice, suggesting that cationic antimicrobial peptides can initiate and regulate adaptive immune responses. It is possible that beta defensins may yfunction similarly. To show this, 100 female, C57BL/6 mice were immunized intranasally on days 0, 7, and 14 with 10 ul (5 ul/nostril) of 0.01 M PBS containing 1 ug HBD1, HBD2, HNP-1, HNP-2 with and without 50 ug OVA. At 21 days, mice were sacrificed, and OVA-specific antibodies were determined in saliva, serum, nasal wash, BAL fluid, and fecal extracts by ELISA. Standards from murine myeloma cells secreting IgM, IgG1, IgG2a, IgG2b, IgG3, IgM, and IgA were used at concentrations of 0, 4, 8, 16, 32, and 64 ng/ml. OVA-specific IgA was not detected in saliva, serum, nasal wash, BAL Lfluid, or fecal extracts in any group, and OVA-specific IgM was detected only in serum. OVA-specific IgG responses were detected in serum, BAL fluid, and fecal extracts only. A trend toward an enhanced OVA-specific IgG response was seen in serum, BAL fluid, and fecal extracts by both HNPs and HBDs that was similar to that reported by Lillard et al. (Proc. Natl. Acad. Sci. U S A 96:651-656, 1999). Supernatants from OVA-stimulated splenic lymphoid cell cultures from mice immunized with HBD + OVA contained high levels of IFN gamma. These results are consistent with the induction of Th1 and Th2-like responses and suggest that HBDs can induce host- adaptive immunity in vivo. We speculate that specific HNPs and HBDs will have preferential activity over others in inducing adaptive immune responses.