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Infection and Immunity, July 2002, p. 3557-3565, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3557-3565.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mechanisms of Monophosphoryl Lipid A Augmentation of Host Responses to Recombinant HagB from Porphyromonas gingivalis

Qiu-Bo Yang,1 Michael Martin,1 Suzanne M. Michalek,1,2 and Jannet Katz2*

Department of Microbiology,1 Department of Oral Biology, University of Alabama at Birmingham, Birmingham, Alabama 352942

Received 21 December 2001/ Returned for modification 21 February 2002/ Accepted 18 April 2002

Porphyromonas gingivalis, a gram-negative, black-pigmented anaerobe, is among the microorganisms implicated in the etiology of adult periodontal disease. This bacterium possesses a number of factors, including hemagglutinins, of potential importance in virulence. Our laboratory has shown the induction of protection to P. gingivalis infection after subcutaneous immunization with recombinant hemagglutinin B (rHagB). The purpose of this study was to determine if humoral antibody responses are induced after intranasal (i.n.) immunization of rHagB and if monophosphoryl lipid A (MPL), a nontoxic derivative of the lipid A region of lipopolysaccharide, acts as a mucosal adjuvant and potentiates responses to rHagB. Further, the effects of MPL on the nature of the response to HagB and on the costimulatory molecules B7-1 and B7-2 on different antigen-presenting cells (APC) were evaluated. Groups of BALB/c mice were immunized three times (2-week intervals) by the i.n. route with HagB (20 µg) alone or with MPL (25 µg). A group of nonimmunized mice served as control. Serum and saliva samples were collected prior to immunization and at approximately 2-week intervals and evaluated for serum immunoglobulin G (IgG) and IgG subclass and for salivary IgA antibody activity by enzyme-linked immunosorbent assay. Mice immunized with rHagB plus MPL had significantly higher salivary IgA (P < 0.05) and serum IgG (P < 0.05) anti-HagB responses than mice immunized with rHagB alone. The IgG1 and IgG2a subclass responses seen in mice immunized with rHagB plus MPL were significantly higher (P < 0.05) than those seen in mice immunized with rHagB only. Further, the IgG2a/IgG1 ratio in the latter group was {approx}1, whereas in mice immunized with rHagB plus MPL the ratio was <1. These results provide evidence for the participation of T helper (Th) 1 and Th2 cells in responses to rHagB and that MPL potentiates a type 2 response to HagB. MPL was also shown to preferentially up-regulate B7-2 expression on B cells, whereas a preferential increase in B7-1 costimulatory molecule was seen on macrophages and dendritic cells. These results provide evidence that MPL exerts a differential regulation in the expression of costimulatory molecules on APC.

* Corresponding author. Mailing address: Departments of Microbiology and Oral Biology, University of Alabama at Birmingham, 845 19th St. South, BBRB 713/5, Birmingham, AL 35294-2170. Phone: (205) 934-2878. Fax: (205) 934-1426. E-mail: jenny_katz{at}micro.microbio.uab.edu.

Editor: J. D. Clements

Infection and Immunity, July 2002, p. 3557-3565, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3557-3565.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Song, H., Belanger, M., Whitlock, J., Kozarov, E., Progulske-Fox, A. (2005). Hemagglutinin B Is Involved in the Adherence of Porphyromonas gingivalis to Human Coronary Artery Endothelial Cells. Infect. Immun. 73: 7267-7273 [Abstract] [Full Text]  
  • Zhang, P., Martin, M., Michalek, S. M., Katz, J. (2005). Role of Mitogen-Activated Protein Kinases and NF-{kappa}B in the Regulation of Proinflammatory and Anti-Inflammatory Cytokines by Porphyromonas gingivalis Hemagglutinin B. Infect. Immun. 73: 3990-3998 [Abstract] [Full Text]  
  • Zhang, P., Martin, M., Yang, Q.-B., Michalek, S. M., Katz, J. (2004). Role of B7 Costimulatory Molecules in Immune Responses and T-Helper Cell Differentiation in Response to Recombinant HagB from Porphyromonas gingivalis. Infect. Immun. 72: 637-644 [Abstract] [Full Text]  
  • Martin, M., Michalek, S. M., Katz, J. (2003). Role of Innate Immune Factors in the Adjuvant Activity of Monophosphoryl Lipid A. Infect. Immun. 71: 2498-2507 [Abstract] [Full Text]  


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