Nicholas H. Carbonetti, PhD

Carbonetti, NH, Wirsing von König, CH, Lan, R, Jacob-Dubuisson, F, Cotter, PA, Deora, R, Merkel, TJ, van Els, CA, Locht, C, Hozbor, D, Rodriguez, ME (2016) Highlights of the 11^th International Bordetella Symposium: From Basic Biology to Vaccine Development. Clinical and Vaccine Immunology 23(11):

Wang, X, Shaw, DK, Hammond, HL, Sutterwala, FS, Rayamajhi, M, Shirey, KA, Perkins, DJ, Bonventre, JV, Velayutham, TS, Evans, SM, Rodino, KG, VieBrock, L, Scanlon, KM, Carbonetti, NH, Carlyon, JA, Miao, EA, McBride, JW, Kotsyfakis, M, Pedra, JHF (2016) The prostaglandin E₂-EP3 receptor axis regulates Anaplasma phagocytophilum-mediated NLRC4 inflammasome activation. PLoS Pathogens 12:e1005803 PMCID: PMC4970705

Carbonetti, NH (2016) Bordetella pertussis: New concepts in pathogenesis and treatment. Current Opinion in Infectious Diseases 29:287-294 PMCID: PMC4846492

Guevara, C, Mooi, FR, Greenberg, DP, Decker, MD, Carbonetti, N, Starner, TD, McCray, PB, Iqbal, J, Gómez-Duarte, OG (2016) Primary human airway epithelial cells: a model to study Bordetella pertussis fimbrial-mediated adherence. Infectious Diseases 48:177-188

Scanlon, KM, Skerry, C, Carbonetti, NH (2015) Novel therapies for the treatment of whooping cough. Pathogens and Disease 73:ftv074 PMCID: PMC4626598

Connelly, C, Sun, Y, Carbonetti, NH (2012) Pertussis toxin exacerbates and prolongs airway inflammatory responses during Bordetella pertussis infection. Infection & Immunity 80:4317-4332 PMCID: PMC3497438

Worthington, ZEV, van Rooijen, N, Carbonetti, NH (2011) Enhancement of Bordetella parapertussis infection by Bordetella pertussis in mixed infection of the respiratory tract. FEMS Immunology and Medical Microbiology 63:119-128 PMCID: PMC3170498

Ayala, VI, Teijaro, JR, Farber, DL, Dorsey, SG, Carbonetti, NH (2011) Bordetella pertussis infection exacerbates influenza virus infection through pertussis toxin-mediated suppression of innate immunity. PLoS ONE 6(4): e19016 PMCID: PMC3080395

We are interested in the pathogenesis of infection and disease caused by Bordetella pertussis, the agent of pertussis or whooping cough. We use adult and infant animal models and in vitro approaches to investigate this host-pathogen interaction, with an emphasis on the host response and age-dependent outcomes. Current projects include the following:

1. Role of interferons in lung inflammatory pathology caused by Bordetella pertussis infection. We identified the type I and III IFN receptors as significant activators of lung gene upregulation during peak B. pertussis infection. We are studying the activation of type I and III IFN expression and their link to lung inflammatory pathology in adult and neonatal mouse models.
2. Sphingosine-1-phosphate receptors as potential therapeutic targets for treatment of pertussis. Sphingosine-1-phosphate (S1P) signals through G protein-coupled receptors (GPCRs) that are sensitive to PT inhibition. We hypothesized that PT inhibits signaling through this receptor that would normally attenuate inflammation after infection, thereby exacerbating inflammation. Treatment of B. pertussis-infected mice with S1P receptor ligands dramatically reduced cytokine production and lung inflammatory pathology, and treatment of B. pertussis-infected neonatal mice reduced lethality, identifying another potential therapeutic avenue for pertussis treatment. However, these effects were not inhibited by PT, and we are currently attempting to dissect the molecular mechanism by which these ligands cause their effect.
3. Neonatal mice infection with Bordetella pertussis as a model of critical pertussis in human infants. As in humans, neonatal mice are susceptible to fatal B. pertussis infection. We found that this lethality is completely dependent on PT activity and that the pathogenesis of disease is quite different from that caused by B. pertussis infection in adult mice. Lack of induction of interferons in response to infection may contribute to susceptibility to lethal infection.

NIH/NIAID R01 AI141372 Age-dependent role of type I interferon in Bordetella pertussis pathogenesis 9/19/18 - 8/31/23 (PI: Carbonetti, NH)

NIH/NIAID R21 AI140035 PGLYRP4 in S1P receptor agonist-mediated attenuation of pertussis disease 1/7/19 - 12/31/20 (PI: Skerry, C - role: collaborator)

NIH/NIAID R21 AI151485 Age-related skewing of angiotensin II signaling potentiates B. pertussis-induced pulmonary hypertension 1/24/20 - 12/31/21 (PI: Scanlon, K - role: collaborator)

• 2019-present: University of Maryland School of Medicine Executive Committee, Basic Science Faculty Representative
• 2019: Scientific Organizing Committee, 12^th International Bordetella Symposium, Brussels, Belgium, April 9-12, 2019 - Chair, Immune Responses session
• 2018-2019: President, Maryland Branch, American Society for Microbiology
• 2017-2019: Deputy Editor-in-chief, Pathogens and Disease
• 2017: Chair, ZGM1 MBRS-SCORE Study Section, NIH
• 2016: Scientific Organizing Committee, 11^th International Bordetella Symposium, Buenos Aires, Argentina, April 5-8, 2016 – Chair, Immune Responses session; Chair, Pertussis Vaccines Roundtable Discussion session
• 2014: Chair, ZGM1 MBRS-SCORE Study Section, NIH
• 2013-present: Editor, Pathogens and Disease
• 2010: Organizing Committee Chair and Host, 9^th International Bordetella Symposium, Baltimore, MD, Sept 30 - Oct 3, 2010
• 2009-present: Editorial Board Member, Infection and Immunity