Lee M. Wetzler, MD
Professor
Boston University School of Medicine
Dept of Medicine
Infectious Diseases Section

MD, State University of New York Upstate Medical University



Dr. Wetzler’s laboratory investigates innate and adaptive immunity and microbial pathogenesis, especially in regards to vaccine development. One major aspect of this work centers on the pathogenic Neisseria, Neisseria gonorrhoeae and Neisseria meningitidis. He has found that the major outer membrane protein of these organisms, the Neisserial porin PorB, can work as an immune adjuvant due to it recognition by the pattern recognition receptor TOLL-like receptor (TLR) 2. He has found that antigen presenting cells, including B cells, dendritic cells and macrophages, are activated by PorB in a TLR2 , TLR1 and MyD88 dependent manner, inducting upregulation of class II MHC, costimulatory molecule CD86 and other markers of activation. Moreover, MAPK signaling events are required for the upregulation of the expression of these markers, as well as production of pro-inflammatory cytokines. Moreover, using an in vivo peritoneal mouse model of inflammation, we have shown that both PorB and intact N. meningitidis induce a significant cellular infux and pro-inflammatory cytokine production, which is also TLR2 dependent. However, we also found that mast cells are activated during this process, which may be in a TLR2 independent manner, along with a significant influx of eosinophils, indicative of induction of a TH2 type cellular response. Studies are continuing to investigate the mechanisms of these phenomena.

We are also investigating the use of this TLR2 ligand, PorB, as a vaccine adjuvant using classic antigens like OVA and more relevant antigens like bacterial capsular polysaccharide. This work has also been extended to investigate the adjuvant activity and mechanism of immune stimulation of the B subunit of cholera toxin. We have found that CTB induces antigen presenting cell stimulation via the lipid raft ganglioside GM1 via induction of a cell-signaling program ending in NF-kB and CREB activation and gene transcription. This work is still on going.

Finally, a new major thrust of the Wetzler lab is investigating the immune response and natural history of Francisella tularensis pulmonary infection in mice and using this data to aid in developing vaccines towards this potential bio-terrorist agent. We have found that using PorB as an adjuvant and Francisella LPS as an atigne, we can enhance protection in these mice, which is likely due to induction of antibodies and improved immunity (potentially both innate and adaptive immunity. It appears that induction of IL-1beta may be more associated with survival bith during natural infection and after vaccination, while IL-6 and IL-17 may have the opposite effect, being more associated with death after pulmonary infection. Finally we have recently found that induction of bronchial associated lymphoid tissue (BALT) after vaccaitnion also appears to be associated with protection. These iBALT structures are long lasting and may be due to persistent antigen stimulation, which we are currently investigating.

Graduate Faculty (Primary Mentor of Grad Students)
Boston University School of Medicine, Division of Graduate Medical Sciences


Professor
Boston University School of Medicine
Microbiology


Active Staff Privileges
Boston Medical Center
Medicine
Infectious Diseases Section



Boston University Inflammatory Disorders Training Grant
09/15/2011 - 08/31/2017 (PI)
NIH/National Institute of Allergy & Infe
5T32AI089673-05

Role of the Innate Immune System in Pathogen-Induced Chronic Inflammation
08/01/2010 - 07/31/2017 (PI of Sub-Project / SP)
PI: Caroline A. Genco, PhD
NIH/National Institute of Allergy & Infe
5P01AI078894-05


Neisserial porins and antigen presenting cells
09/01/2016 - 08/31/2020 (PI)
NIH-NIAID
2R01AI040944-19A1

Gonococcal Vaccine Evaluation in a Humanized Mouse Model
07/17/2013 - 06/30/2018 (PI)
NIH-NIAID
4R01AI103400-04

Gonococcal Vaccine Evaluation in a Humanized Mouse Model
07/17/2013 - 06/30/2018 (PI)
NIH-NIAID
5R01AI103400-03

Neisserial porins and antigen presenting cells
09/01/2015 - 08/31/2016 (PI)
NIH-NIAID
2R56AI040944-19

Neisserial Porins and Antigen Presenting Cells
09/01/2010 - 08/31/2015 (PI)
NIH-NIAID
5R01 AI040944-18

Characterization of a cell free recombinant gonococcal porin
09/01/2014 - 06/30/2015 (PI)
SutroVax, Inc.

Core C - Role of Innate Immune System in Pathogen Induced Chronic Inflammation
08/01/2010 - 06/30/2015 (PI)
Trustees of Boston University NIH-NIAID

Neisserial Porins and Antigen Presenting Cells
09/01/2006 - 08/31/2010 (PI)
NIH-NIAID
5R01 AI040944-13

Immuno - Prophylaxis - Core A: Animals (Tularemia - Murphy)
09/15/2003 - 02/28/2009 (PI)
NIH-NIAID
5 U19 AI056543-05 (A)

Immuno-Prophylaxis - Project 1: Vaccines (Tularemia - Murphy)
09/15/2003 - 02/28/2009 (PI)
NIH-NIAID
5 U19 AI056543-05 (A)

Showing 10 of 17 results. Show All Results


Yr Title Project-Sub Proj Pubs
2016 Gonococcal Vaccine Evaluation in a Humanized Mouse Model 4R01AI103400-04 1
2016 Neisserial porins and antigen presenting cells 2R01AI040944-19A1 20
2015 Boston University Inflammatory Disorders Training Grant 5T32AI089673-05 7
2015 Neisserial porins and antigen presenting cells 2R56AI040944-19
2014 Gonococcal Vaccine Evaluation in a Humanized Mouse Model 5R01AI103400-02 1
2014 Neisserial Porins and Antigen Presenting Cells 5R01AI040944-18 20
2014 Animal Core 5P01AI078894-05-7799 22
2013 Gonococcal Vaccine Evaluation in a Humanized Mouse Model 1R01AI103400-01A1 1
2013 Neisserial Porins and Antigen Presenting Cells 5R01AI040944-17 20
2013 Animal Core 5P01AI078894-04-7799 22
Showing 10 of 48 results. Show All Results
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

  1. Reiser ML, Mosaheb MM, Lisk C, Platt A, Wetzler LM. The TLR2 Binding Neisserial Porin PorB Enhances Antigen Presenting Cell Trafficking and Cross-presentation. Sci Rep. 2017 Apr 07; 7(1):736. PMID: 28389664; DOI: 10.1038/s41598-017-00555-4;.
  2. Mosaheb MM, Reiser ML, Wetzler LM. Toll-Like Receptor Ligand-Based Vaccine Adjuvants Require Intact MyD88 Signaling in Antigen-Presenting Cells for Germinal Center Formation and Antibody Production. Front Immunol. 2017; 8:225.View Related Profiles. PMID: 28316602; DOI: 10.3389/fimmu.2017.00225;.
  3. Wetzler LM, Feavers IM, Gray-Owen SD, Jerse AE, Rice PA, Deal CD. Summary and Recommendations from the National Institute of Allergy and Infectious Diseases (NIAID) Workshop "Gonorrhea Vaccines: the Way Forward". Clin Vaccine Immunol. 2016 Aug; 23(8):656-63. PMID: 27335384; PMCID: PMC4979170; DOI: 10.1128/CVI.00230-16;.
  4. Toussi DN, Wetzler LM, Liu X, Massari P. Neisseriae internalization by epithelial cells is enhanced by TLR2 stimulation. Microbes Infect. 2016 Oct; 18(10):627-638.View Related Profiles. PMID: 27373686; DOI: 10.1016/j.micinf.2016.06.001;.
  5. Xu F, Reiser M, Yu X, Gummuluru S, Wetzler L, Reinhard BM. Lipid-Mediated Targeting with Membrane-Wrapped Nanoparticles in the Presence of Corona Formation. ACS Nano. 2016 Jan 26; 10(1):1189-200.View Related Profiles. PMID: 26720275; PMCID: PMC4842014; DOI: 10.1021/acsnano.5b06501;.
  6. Islam EA, Shaik-Dasthagirisaheb Y, Kaushic C, Wetzler LM, Gray-Owen SD. The reproductive cycle is a pathogenic determinant during gonococcal pelvic inflammatory disease in mice. Mucosal Immunol. 2016 Jul; 9(4):1051-64. PMID: 26693700; PMCID: PMC4915993; DOI: 10.1038/mi.2015.122;.
  7. Massari P, Gunawardana J, Liu X, Wetzler LM. Correction for Massari et al., meningococcal porin PorB prevents cellular apoptosis in a Toll-like receptor 2- and NF-?B-independent manner. Infect Immun. 2015 Aug; 83(8):3339.View Related Profiles. PMID: 26157088; PMCID: PMC4496629; DOI: 10.1128/IAI.00627-15;.
  8. Barlam TF, Morgan JR, Wetzler LM, Christiansen CL, Drainoni ML. Antibiotics for respiratory tract infections: a comparison of prescribing in an outpatient setting. Infect Control Hosp Epidemiol. 2015 Feb; 36(2):153-9.View Related Profiles. PMID: 25632997; DOI: 10.1017/ice.2014.21;.
  9. Kramer CD, Weinberg EO, Gower AC, He X, Mekasha S, Slocum C, Beaulieu LM, Wetzler L, Alekseyev Y, Gibson FC, Freedman JE, Ingalls RR, Genco CA. Distinct gene signatures in aortic tissue from ApoE-/- mice exposed to pathogens or Western diet. BMC Genomics. 2014; 15:1176.View Related Profiles. PMID: 25540039; PMCID: PMC4367889; DOI: 10.1186/1471-2164-15-1176;.
  10. Kattner C, Toussi DN, Zaucha J, Wetzler LM, Rüppel N, Zachariae U, Massari P, Tanabe M. Crystallographic analysis of Neisseria meningitidis PorB extracellular loops potentially implicated in TLR2 recognition. J Struct Biol. 2014 Mar; 185(3):440-7.View Related Profiles. PMID: 24361688; PMCID: PMC3943661; DOI: 10.1016/j.jsb.2013.12.006;.
Showing 10 of 73 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 73 publications over 28 distinct years, with a maximum of 6 publications in 2005

YearPublications
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In addition to these self-described keywords below, a list of MeSH based concepts is available here.

Adjuvants
Francisella
Infections Diseases
Innate Immunity
Neisseria
Vaccines
Immunology
STDs
Meningitis
Travel Medicine

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650 Albany St Evans Biomed Research Ctr
Boston MA 02118
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