The Virulence Factors of Bordetella pertussis : Talented Modulators of Host Immune Response
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REVIEW
The Virulence Factors of Bordetella pertussis: Talented Modulators of Host Immune Response Giorgio Fedele • Manuela Bianco • Clara Maria Ausiello
Received: 28 December 2012 / Accepted: 4 August 2013 Ó L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2013
Abstract Approximately 40 million whooping cough cases and between 200,000 and 400,000 pertussis-linked deaths are recorded each year. Although several types of vaccines are licensed and widely used, Bordetella pertussis continues to circulate in populations with high vaccine coverage of infants and children due to the waning of protection induced by the vaccination. B. pertussis typically expresses a wide array of virulence factors which promote bacterial adhesion and invasion by altering the local environment, including pertussis toxin, tracheal cytotoxin, adenylate cyclase toxin, filamentous hemagglutinin, and the lipooligosaccharide. The virulence factors of B. pertussis also possess immunomodulatory properties, exerted through their enzymatic and receptor-binding activities. Both pro- and anti-inflammatory effects are mediated, that can subvert host innate and adaptive immunity and favor the onset of a long-term infection. This review describes the capacities of B. pertussis virulence factors to modulate host immune responses and the mechanisms employed, which have been the subject of extensive research in the recent years, both in murine and human experimental systems. Knowledge of these mechanisms is gaining increasing importance, since it could provide in the near future the basis for the identification of
G. Fedele (&) M. Bianco C. M. Ausiello Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanita`, Viale Regina Elena, 299, 00161 Rome, Italy e-mail: [email protected] Present Address: M. Bianco Research Development, Novartis Vaccines and Diagnostics srl, Siena, Italy
therapeutic agents for modulating the immune system as well as novel molecular targets to treat pertussis. Keywords Bordetella pertussis Macrophages Dendritic cells T cell response Cytokines Airways epithelium
Introduction Bordetella pertussis, a Gram-negative coccobacillus and strict human pathogen of the respiratory tract, is the causative agent of pertussis or whooping cough, the fifth largest cause of vaccine-preventable death in children under 5 years of age (Ulloa-Gutierrez et al. 2011). Approximately, 40 million whooping cough cases and between 200,000 and 400,000 pertussis-linked deaths are recorded each year (Crowcroft et al. 2003; Leung et al. 2007). The substantial majority of pertussis deaths occur in developing countries, due to inadequate vaccination coverage (Ulloa-Gutierrez et al. 2011). However, pertussis has not only persisted, but even resurged in recent years in countries with highly vaccinated populations, where annual infection rates can reach 1–7 % and epidemic episodes have been recorded (Cherry 2012; de Melker et al. 2006; Ward et al. 2006). Resurgence of pertussis in c
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