WETZLER LABORATORY
Evans
Biomedical Research Center
Boston Medical Center
Boston University School of Medicine
My laboratory is interested in
bacterial pathogenesis and the generation of protective immune responses.
Our work mainly centers on the pathogenic neisseria, Neisseria gonorrhoeae
and Neisseria meningitidis. We have been using the major outer
membrane protein of the neisseria, termed porins, as potential vaccine
candidates. We are currently involved in a collaboration with the Rockefeller University, the
University of North Carolina and the NIH in beginning human trials with a
potential anti-gonococcal vaccine utilizing the gonococcal porins inserted in
liposomes. A unique property of these porins
is their ability to act as immune stimulators and augment the immune response
to poorly immunogenic substances. We have characterized this ability and
are currently investigating the mechanism behind their immunpotentiating
(adjuvant) effects. We believe that it is likely due to their affect on
antigen presenting cells, increasing various ligands (especially one called
B7-2) and inducing B cell proliferation and immunoglobulin secretion.
Studies are ongoing investigating the relationship between these findings and
the adjuvanticity of the porins. Interestingly, these porins have an
effect on the susceptibility of cells to apoptosis, mainly by associating with
and stabilizing mitochondrial membranes. We are investigating this
phenomena along with investigating the signal transduction events induced by
the porins. We have found that
Neisserial porins stimulate B cells by inducing NF-kB nuclear translocation and by inducing protein
tyrosine kinase activaity and by activating MAPK Erk1 and Erk2.
Another group of studies we are performing is
characterizing the relationship between the immune response to gonococcal
porins in patients and partners of patients with gonococcal disease and
possible protective immunity. We are measuring the T cell response in
female partners of men with gonorrhea and relating these findings to whether
the female partners in turn get gonorrhea. This is being performed as
part of the STD-CRC program project grant that our division has received.
Other projects include
lymphocyte homing and induction of mucosal immunity in patients with gonococcal
infection and the development
of an animal model for Neisserial disease utlizing transgenic mice.
In addition to my position
as Associate Professor in the Division of Infectious Diseases and Department of
Medicine, I am a member of the Department
of Microbiology and the Immunology
Training Program and the Host
Pathogen Interaction Training Program at the Boston University School of Medicine.
Bjerknes, R., Guttormsen, H-K., Solberg, C.O., Wetzler, L.M., 1995, Neisserial porins inhibit human neutrophil actin polymerization, degranulation, opsonin receptor expression and phagocytosis, but prime the neutrophils to increase oxidative burst, Infection and Immunity, 63:160-167 (PubMed Citation)
Blake, M.S., and Wetzler, L.M., 1995, Vaccines for gonorrhea: where are we on the curve?, Trends in Microbiol., 3:469-474 (PubMed Citation)
Wetzler, L.M., Ho, Y. and Reiser, H., 1996, Neisserial porins induce B lymphocytes to express costimulatory B7-2 molecules and to proliferate, J. Exp. Med, 183:1151-1159 (PubMed Citation)
Gill, M.J., McQuillen, D.P., van Putten, J.P.M., Wetzler, L.M., Bramley, J., Crooke, H., Parsons, N.J., Cole, J.A., and Smith H., 1996, Functional characterization of a sialylytransferase deficient mutant of Neisseria gonorrhoeae, Infection and Immunity, 64:3374-3378 (PubMed Citation)
Snapper, C.M., Rosas, F.R., Kehry, M.R., Mond, J.J., and Wetzler, L.M., 1997 Induction of B Lymphocyte Proliferation and Immunoglobulin Secretion by Neisserial Porins, Infection and Immunity, 65:3203-3208 (PubMed Citation)
Næss, L.M., Oftung, F., Aase, A., Wetzler, L.M., Sandin, R., and Michaelsen, T.M., 1998 Cellular immune response after immunization with the Norwegian group B Neisseria meningitidis outer membrane vesicle vaccine, Infection and Immunity, 66:959-965 (PubMed Citation)
Guttormsen, H-K., Wetzler, L.M., Finberg, R., and Kasper, D., 1998 Immunologic Memory induced by glycoconjugate vaccine in a murine adoptive transfer model, Infection and Immunity, 66:2026-2032 (PubMed Citation)
Henriksen, A.Z., Mæland, J.A., and Wetzler, L.M., 1998, An epitope shared by enterobacterial and neisserial porin proteins, APMIS, 106:818-824 (PubMed Citation)
Oftung, F., Næss, L.M., Wetzler, L.M., Korsvold, G.E., Aase, A., Høiby, A., Dalseg, R., Holst, J., Michaelsen, T.E., and Haneberg, B.. 1999, Antigen specific human T cell responses after nasal immunization with a meningococcal serogroup b outer membrane vesicle vaccine. Infection and Immunity, 67:921-927 (PubMed Citation)
Lehmann, A.K., Halstensen, A., Aaberge, I, Holst, J.,Sørnes, S., Wetzler, L.M., and Guttormsen, H-K., 1999, Human opsonins induced during meningococcal disease recognize PorA and PorB outer membrane proteins. Infection and Immunity, 67:2552-2560 (PubMed Citation)
Simpson, S.D., Ho, Y, Rice, P.A., and Wetzler, L.M., 1999, T cell responses to neisserial porins in patients with gonococcal disease, J. Infect. Dis., 180:762-773 (PubMed Citation)
Mackinnon, F.M, Ho, Y., Blake, M.S., Michon,
F., Chandraker, A., Sayegh, M.H., and Wetzler, L.M., 1999, The role of B/T
costimulatory signals in the adjuvant activity of a conjugate vaccine
containing neisserial porin J.
Infect. Dis. 180:755-761 (PubMed
Citation)
Ram, S., Mackinnon, F.G.,
Gulati, S., McQuillen, D.P., Vogel, U., Frosch, M., Elkins, C., Guttormsen,
H-K., Wetzler, L.M., Opperman, M., Rangburn, M.K., and Rice, P.A., 1999, The
contrasting mechanisms of serum resisitance of Neisseria gonorrhoeae and
group B Neisseria meningitidis, Molecular Immunology, 36:915-928 (PubMed
Citation)
Massari, P. Ho, Y. and.
Wetzler,.L.M, 2000, Neisseria meningitidis porin PorB interacts with
mitochondria and protects cells from apoptosis, Proc. Nat. Acad. Sci.
97:9070-9075 (PubMed
Citation) (full
text PNAS article)
Wedege, E., Bolstad, K., Wetzler, L.M., and
Guttormsen, H-K., 2000 IgG antibody activity against meningococcal class
1 and 3 outer membrane proteins in patient sera: comparison between immunoblot
and ELISA analysis, J. Imm. Methods 244:9-15
Bhasin, N., Ho, Y., and Wetzler, L.M., 2001, Neisseria meningitidis lipopolysaccharide modulates the specific humoral immune repsonse to Neisserial porins but has no effect on porin-inuced upregulation of costimulatory ligand B7-2, Infection and Immunity, 69:5031–5036 (PubMed Citation) (IAI Abstract)
Massari, P., Henneke, P., Ho, Y., Latz, E.,
Golenbock, D. and Wetzler, L.M., 2002, Immune stimulation by Neisserial porin is
TLR2 and MyD88 dependent, J. Immuno.
(Cutting Edge), 168: 1533-1537
(PubMed
Citation)
(full
text JI article)
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