DEFENSIN INDUCED ADAPTIVE IMMUNITY IN MICE AND ITS POTENTIAL IN PREVENTING PERIODONTAL DISEASE

Authors: Brogden, Kim; Heidari, Mohammad; Sacco, Randy; PALMQUIST, DEBRA - UNIV. OF IOWA, IOWA CITY; GUTHMILLER, JANET - UNIV. OF IOWA, IOWA CITY; JOHNSON, GEORGIA - UNIV. OF IOWA, IOWA CITY; JIA, HONG - UNIV. OF IOWA, IOWA CITY; TACK, BRIAN - UNIV. OF IOWA, IOWA CITY; MCCRAY, JR., PAUL - UNIV. OF IOWA, IOWA CITY

Submitted to: Oral Microbiology and Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/11/2002
Publication Date: 1/20/2003
Citation: BROGDEN, K.A., HEIDARI, M., SACCO, R.E., PALMQUIST, D.E., GUTHMILLER, J.M., JOHNSON, G.K., JIA, H.P., TACK, B.F., MCCRAY, JR., P.B. DEFENSIN-INDUCED ADAPTIVE IMMUNITY IN MICE AND ITS POTENTIAL IN PREVENTING PERIODONTAL DISEASE. ORAL MICROBIOLOGY AND IMMUNOLOGY. 2003. v. 18. p. 95-99.

Interpretive Summary: Respiratory tract diseases are a leading cause of loss from disease in the cattle, sheep and goat industries. Annual loss in the United States is estimated to exceed one billion dollars. Losses are from mortality, reduced feed efficiency, and slaughter condemnations, as well as prevention and treatment measures. Novel methods to induce systemic immune responses may reduce these losses. In this study, defensins, as elements of mucosal innate defense, were found to trigger adaptive immune responses to co- administered foreign antigens. To show this, mice were immunized intranasally with defensins (alpha and beta) with and without ovalbumin, a protein antigen. Ovalbumin specific IgG was detected in serum and concentrations were enhanced significantly by defensins. Further work will determine if this mechanism occurs in ruminants with microbial antigens. Corollary benefits include an increase in the profitability and international competitiveness of the U. S. cattle industry, a stronger rural economy, and a continued supply of inexpensive, wholesome beef and beef products for the American consumer.

Technical Abstract: HBDs, as elements of mucosal innate defense, may trigger adaptive immune responses to co-administered foreign antigens. To show this, C57BL/6 mice were immunized intranasally with 10 ul of 0.01 M PBS containing 1 ug HBD1 or HBD2 with and without 50 ug OVA. Mice immunized with 1 ug HNP-1 or HNP-2 with and without 50 ug OVA were used as controls. At 21 days, mice were sacrificed. OVA-specific IgA was not detected in saliva, serum, nasa wash, BAL fluid, and fecal extracts by ELISA and IgM was detected only in serum. OVA-specific IgG was detected in serum (51 ng/ml) and concentrations were enhanced by HNP-1 (319 ng/ml), HBD1 (201 ng/ml), and HBD2 (137 ng/ml) but not by HNP-2 (36 ng/ml). Supernatants from OVA- stimulated splenic lymphoid cell cultures from these mice contained elevated IFN-gamma and IL-10 but not IL-4 and were consistent with the results reported for HNPs. Overall, HBD1 and 2 can induce host-adaptive immunity to co-administered antigens on mucosal surfaces.