Massari, Paola, Ph.D.

Ph.D. and Post-doctoral training: University of Naples “Federico II”, Naples, Italy and Chiron-Biocine, Siena, Italy

Neisseria sp. comprise pathogenic and non-pathogenic organisms that colonize the human nasopharynx. N. lactamica is not associated with disease, except in rare occasions, while N. meningitidis occasionally invades the host, causing fatal meningococcal disease and septicemia. Neisserial components at the immediate bacterial-host cell interface interact with cell surface receptors. Porins are Neisserial major outer membrane proteins (OMPs) expressed in all strains, regardless of pathogenicity, with a significant sequence variability within surface-exposed regions (loops) among strains. PorB is specifically recognized by Toll-like receptor 2 (TLR2) on the host cell surface and induces TLR2-dependent cell activation. The mechanism(s) of TLR2 recognition of PorB is unknown. Similar to Nme PorB, Nlac PorB also binds to TLR2 in vitro and on the cell surface, but the specificity of this interaction is different from Nme PorB. Nlac PorB is less efficient in inducing TLR2-dependent cell activation and TLR2 expression in human airway epithelial cells compared to Nme PorB. These proteins show a significant difference in the sequence of surface exposed loops that are crucial for interaction with TLR2 and subsequent host cell responses. Since the responsiveness of human airway epithelial cells to colonizing organisms is partly regulated via TLR expression and signaling, a commensal organism would benefit from expressing a product that induces a reduced TLR2 expression and TLR2-dependent signaling, likely delaying or avoiding clearance by the host. The Massari group focuses on understanding how modification of PorB surface loops might affect TLR2 signaling, cells activation and outcome of Neisserial infection of airway epithelial cells.

Additional aspects of Dr. Massari’s research also include the mechanisms of immune adjuvanticity of bacterial porins from Neisseriae, Fusobacterium nucleatum (an oral pathogen) and Chlamidya, as well as porins involvement in modulation of apoptosis. Her work with Neisserial porins has described demonstrated that Neisserial porins immune stimulatory ability is related to their interaction with TLR2 and TLR1, which is necessary to activate cells signaling in the target cells, while their ability to modulate host cell apoptosis is by acting on mitochondria and inducing target cells survival after infection.

Selected Publications:

Toussi DN, Liu X, Massari P. 2012. The FomA Porin from Fusobacterium nucleatum Is a Toll-Like Receptor 2 Agonist with Immune Adjuvant Activity. Clin Vaccine Immunol., Jul; 19(7):1093-101. Epub 2012 May 23. [PMID: 22623652] (PMCID in Process)

Arjunaraja S, Massari P, Wetzler LM, Lees A, Colino J, Snapper CM. 2012. The nature of an in vivo anti-capsular polysaccharide response is markedly influenced by the composition and/or architecture of the bacterial subcapsular domain. J. Immunol., Jan 15; 188(2):569-77. Epub 2011 Dec 7. [PMID: 22156342] (PMCID: PMC3253264)

Massari P, Wetzler LM. 2012. Analysis of Parameters Associated with Prevention of Cellular Apoptosis by Pathogenic Neisseriae and Purified Porins. Methods Mol Biol.; 799:319-41. [PMID: 21993654] (PMCID in Process)

Oliveira-Nascimento L, Massari P, Wetzler LM. 2012. The role of TLR2 in infection and immunity. Front Immunol.; 3:79. Epub 2012 Apr 18. [PMID: 22566960] (PMCID: PMC3342043)

Liang YM, Elliot J, Noronha AM, Liu X, Hetzel J, Wetzler LM, Rarick MD, Massari P, Hasturk H, Kantarci A, Winter H, Farraye F, Ganley-Leal LM. 2011. Toll-like receptor 2 induces mucosal homing receptor expression and IgA production by human B cells. Clin Immunol., Jan; 138(1):33-40. Epub 2010 Oct 14. [PMID: 20947433] (PMCID in Process)

Liu X, Wetzler LM, Oliveira Nascimento L, Massari P. 2010. Human airway epithelial cell responses to Neisseria lactamica and purified porin via TLR2-dependent signaling. Infect. Immun., Dec; 78(12):5314-23. Epub 2010 Oct 11. [PMID: 20937766] (PMCID: PMC2981301)

Vaughan AT, Brackenbury LS, Massari P, Davenport V, Gorringe A, Heyderman RS, Williams NA. 2010. Neisseria lactamica Selectively Induces Mitogenic Proliferation of the Naive B Cell pool via Cell Surface Ig. J. Immunol., Sep 15; 185(6):3652-60. Epub 2010 Aug 13. [PMID: 20709949] (PMCID in Process)

Massari P, Gunawardana J, Liu X, Wetzler LM. 2009. Meningococcal porin PorB prevents cellular apoptosis in a TLR2- and NF-{kappa}B-independent manner. Infect. Immun., Mar; 78 (3):994-1003. Epub 2009 Dec 22. [PMID: 20028813] (PMCID: PMC2825956)

Follows SA, Murlidharan J, Massari P, Wetzler LM, Genco CA. 2009. Neisseria gonorrhoeae infection protects human cervical epithelial cells from apoptosis via expression of host anti-apoptotic proteins. Infect. Immun., Sep; 77(9):3602-10. Epub 2009 Jun 22. [PMID: 19546192] (PMCID: PMC2738021)

Liu X, Wetzler LM, Massari P. 2008.The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant. Vaccine., Feb 6; 26(6):786-96. Epub 2007 Dec 26. [PMID: 18191311] (PMCID: PMC2259119)

Massari P, Visintin A, Gunawardana J, Halmen KA, King CA, Golenbock DT, Wetzler LM. 2006. Meningococcal porin PorB binds to TLR2 and requires TLR1 for signaling. J. Immunol., Feb 15; 176(4): 2373‑80. [PMID: 16455995] (PMCID in Process)

Primary teaching affiliate
of BU School of Medicine