Massimo Costalonga

Assistant Professor
Division of Periodontology
Department of Developmental and Surgical Sciences

Address: 18-226 Moos Tower 515 Delaware St. SE Minneapolis, MN 55455 Phone: (612) 626-2466 E-mail: costa002@umn.edu

Education / Training:

Institution		Degree		Year		Field of Study
Universita' degli Studi di Milano Milano, Italy		DMD		1991
University of Minnesota School of Dentistry		Certificate		1998		Periodontology
University of Minnesota Medical School		Postodoctoral Training		2000		Clinical Microbiology and Molecular Biology
University of Minnesota Medical School		Postodoctoral Training		2003		Mucosal Immunology

Research Area / Interests:

Dr. Costalonga and his co-investigator Mark Herzberg, professor in the Department of Diagnostic and Biological Sciences, are completing a three-year R01 grant from the National Institute of Dental and Craniofacial Research to study how commensal microorganisms interact with the immune system at mucosal sites such as the intestine and the airways. Central to Costalonga's research is a mouse model of the immune system that he developed through collaboration with Marc Jenkins and Patrick Cleary, both professors in the Department of Microbiology in the Medical School. Using the adoptive transfer technique pioneered by Jenkins, Costalonga obtains and then transfers mouse T cells that specifically recognize ovalbumin (a foreign protein to mice) into normal mice. These mice are then fed a strain of the commensal bacterium Lactobacillus murinus that has been modified to express ovalbumin. As these bacteria colonize the intestine, the transferred ovalbumin-specific T cells see the bacteria's ovalbumin tag and mount a response. Costalonga subsequently retrieves these T cells and analyzes them for two key responses: proliferation and cytokine production. The results indicate if the immune system is responding to the ovalbumin through cell-mediated immunity (by stimulating macrophages) or antibody production by B cells. He is also examining T cell responses in the nasal lymphoid tissues after administering ovalbumin- tagged L. murinus or Streptococcus pyogenes, a pathogen that can cause rheumatic fever and other serious illnesses. That work addresses a long-term goal of the research, which is to compare the responses to commensal bacteria to those induced by pathogens. In another mouse model, Costalonga is investigating the connection between periodontitis and the immune response to bacteria. Porphyromonas gingivalis causes an inflammatory response that induces bone loss in BALB/c mice, but induces neither inflammation nor bone loss in another strain of mice, C57BL/6. He is studying a protein known as toll-like receptor 4 (TLR4) found on antigen-presenting cells (dendritic cells and macrophages, for example) that is one of the first molecules to interact with P. gingivalis. Costalonga wants to understand how the cascade of events that culminates in bone resorption is initiated by TLR4-P. gingivalis binding. Early results with TLR4-deficient mice indicate that the effects of the bacteria on bone loss can be modulated based on TLR4 expression. In time, he plans to use the adoptive transfer technique to study T and B cell responses that may contribute to bone loss in these mice.

Selected Publications:

Selected peer-reviewed publications Costalonga M, Herzberg MC, Zhao Z, Fischer L. Cleary PP. Intranasal delivery of commensals or invasive pathogens induces effector Th1 cells but not Th2 differentiation or T regulatory cells in vivo. Manuscript in preparation Costalonga M, Herzberg MC, Zhao Z, Fischer L. Commensal microbes transmucosally activate antigen-specific CD4 T cells in vivo. Manuscript in preparation Costalonga M, Batas L, Reich BJ. Dual effect of TLR-4 in Porphyromonas gingivalis-induced bone loss. Journal of Dental Research. Manuscript accepted with revisions Costalonga M, Zell T. Lipopolysaccharide enhances in vivo IL-2 production and proliferation by naïve antigen-specific CD4 T cells via a TLR4-dependent mechanism. Immunology. In Press 2007 Medaglini D, Ciabattini A, Cuppone AM, Costa C, Ricci S, Costalonga M, Pozzi G. In vivo activation of naive CD4+ T cells in nasal mucosa-associated lymphoid tissue following intranasal immunization with recombinant Streptococcus gordonii. Infection and Immunity. 2006 May;74(5):2760-6. Park HS, Costalonga M, Reinhardt RL, Dombek PE, Jenkins MK, Cleary PP. Primary induction of CD4 T cell responses in nasal associated lymphoid tissue during group A streptococcal infection. Eur J Immunol. 2004 Oct;34(10):2843. McSorley SJ, Asch S, Costalonga M, Reinhardt RL, Jenkins MK. Tracking Salmonella-specific CD4 T cells in vivo reveals a local mucosal response to systemic infection. Immunity 2002 Mar;16(3):365-77. Costalonga M, J. S. Hodges, Herzberg MC. Streptococcus sanguis Modulates Transmucosally Type II Collagen -induced Arthritis in DBA/1J Mice. The Journal of Immunology 2002 Aug 15;169(4):2189-95 Abstracts Zhao Z., Fischer L., Herzberg, M.C., Costalonga M. Effector Cytokines in Mucosally-Primed Lymphocytes Specific for Commensals and Pathogens. Abstract ID#93082. Submitted to the IADR/AADR/CADR 85th General Session. Costalonga M, Zhao Z. Mucosal T cell activation against commensals in vivo. Proceedings of the Society of Mucosal Immunology 12th International Meeting ¿ Boston, MA Costalonga M and Zhao Z. Kinetics of mucosal T cell activation against commensals in vivo. J. Dent. Res. 2005 Vol. 84 Special Issue A. Abstract # 1502 Batas L, Hodges J and Costalonga M. TLR-4 pathway in a murine periodontitis model. J. Dent. Res. 2005 Vol. 84 Special Issue A. Abstract # 1130 Costalonga M and Jenkins MK. TLR4 enhances clonal expansion of CD4+ T cells. Abstract #101 - IADR/AADR/CADR 82nd General Session (March 10-13, 2004) Costalonga M, Herzberg MC, Cleary PP, Jenkins MK. Tracking Mucosal T Cells Specific for Commensal Microbes in Vivo. J. Dent. Res. 81 (Special Issue A - Abstract #2485):A-313, 2001 Costalonga M, Cue D, Cleary PP, Jenkins MK. Ovalbumin-specific T cells recognize Lactobacillus murinus expressing an ovalbumin T cell epitope in vivo. J. Dent. Res. 80 (Special Issue Abstract #710):36-267, 2001. Costalonga M. ¿Streptococcus sanguis modulates autoimmune arthritis in mice.¿ Doctor of Philosophy Thesis, Field: Oral Biology - University of Minnesota, Minneapolis MN Costalonga M, Herzberg MC. S. sanguis fed to neonatal DBA/1 mice modulate collagen-induced arthritis. (Abstract # 21.22) 10th International Congress of Mucosal Immunology. Amsterdam, The Netherlands, 27 June-1 July, 1999. Proceedings and abstracts. Immunology Letters 1999. 69(1): p. 1-216. M. Costalonga, M. C. Herzberg. T cell cross reactivity between the arthritogenic epitope of type II collagen and Streptococcus sanguis strain 133-79. J. Dent. Res. 78 (Special Issue Abstract #2782): 453, 1999. M. Costalonga, J. S. Hodges, M. C. Herzberg. Orally Administered Streptococcus sanguis Modulates Autoimmune Arthritis in Mice. J. Dent. Res. 1998. Vol. 77 (Special Issue B Abstract # 1296): 793 Oral presentation. 76th General Session of the International Association of Dental Research, June 24-27, 1998, Nice, France. M.J. Szurek, M. Costalonga, M. C. Herzberg. Streptococcus sanguis Feeding Stimulates Mesenteric Lymphocytes in DBA/1 Mice. J. Dent. Res. 1998. Vol. 77B: 729 Abstract # 782 - Poster presentation. 76th General Session of the International Association of Dental Research, June 24-27, 1998, Nice, France.

Brief Biographical Data: