Defensins attenuate cytokine responses yet enhance antibody responses to Porphyromonas gingivalis adhesins in mice.
OBJECTIVE
Our aim is to assess the ability of human neutrophil peptide alpha-defensins (HNPs) and human beta-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.


METHODS
In the first study, C57BL/6 mice were given 10 microg rHagB or rFimA without and with 1 microg 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 microg rHagB or rFimA without and with 1 microg 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.


CONCLUSIONS
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.
Kohlgraf
Karl G
KG
Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA. karl-kohlgraf@uiowa.edu
Ackermann
Abbey
A
Lu
Xiaoying
X
Burnell
Kindra
K
Bélanger
Myriam
M
Cavanaugh
Joseph E
JE
Xie
Hua
H
Progulske-Fox
Ann
A
Brogden
Kim A
KA
D018829:Adhesins, Bacterial / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis*; D016866:Bacteroidaceae Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors*; D005260:Female; D036781:Fimbriae Proteins / Q000276:immunology*; D006801:Humans; D037102:Lectins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009296:Nasal Cavity / Q000276:immunology; D016966:Porphyromonas gingivalis / Q000276:immunology; D012463:Saliva / Q000276:immunology; D044967:Serum / Q000276:immunology; D023084:alpha-Defensins / Q000276:immunology*; D023083:beta-Defensins / Q000276:immunology*
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D016207:Cytokines; C098582:HagB protein, Porphyromonas gingivalis; D037102:Lectins; D023084:alpha-Defensins; D023083:beta-Defensins; C063055:fimbrillin; D036781:Fimbriae Proteins