Defensins attenuate cytokine responses yet enhance antibody responses to Porphyromonas gingivalis adhesins in mice

Abstract

Aim: Our aim is to assess the ability of human neutrophil peptide α-defensins (HNPs) and human β-defensins (HBDs) to attenuate proinflammatory cytokine responses and enhance antibody responses to recombinant hemagglutinin B (rHagB) or recombinant fimbrillin A (rFimA) from Porphyromonas gingivalis 381 in mice. Materials & methods: In the first study, C57BL/6 mice were given 10 µg rHagB or rFimA without and with 1 µg HNP1, HNP2, HBD1, HBD2 or HBD3. At 24 h, mice were euthanized and cytokine concentrations were determined in nasal wash fluid (NWF), bronchoalveolar lavage fluids, saliva and serum. In the second study, C57BL/6 mice were given 10 µg rHagB or rFimA without and with 1 µg HNPs or HBDs similarly on days 0, 7 and 14. At 21 days, mice were euthanized and rHagB- and rFimA-specific antibody responses were determined in NWF, bronchoalveolar lavage fluids, saliva and serum. Results: Mice given rHagB + HNP2, rHagB + HBD1 and rHagB + HBD3 produced significantly lower (p < 0.05) IL-6 responses than mice given rHagB alone. Mice given rHagB + HNP1, rHagB + HNP2, rHagB + HBD1 and rHagB + HBD3 produced significantly lower (p < 0.05) keratinocyte-derived chemokine responses than mice given rHagB alone. Mice given rFimA produced very low levels of IL-6 and only moderate levels of keratinocyte-derived chemokine in NWF that were not attenuated by prior incubation of rFimA with any defensin. Mice given rHagB + HNP1 produced a significantly higher (p < 0.05) serum IgG antibody response than mice given rHagB alone and mice given rFimA + HNP2 produced a higher, but not significant, antibody response. Conclusion: The ability of HNPs and HBDs to attenuate proinflammatory cytokine responses in murine NWF and enhance IgG antibody responses in serum was dependent upon both the defensin and antigen of P. gingivalis.