Investigating Pertussis Toxin and its Impact on Vaccination

Coutte, Loïc; Locht, Camille

doi:10.2217/fmb.14.123

Cited by 17 publications

(15 citation statements)

References 117 publications

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“…Those authors also found that lethality was reduced upon infection by B. pertussis strains with undefined transposon insertions putatively reducing secretion of pertussis toxin (PT) (15,16). PT, a secreted virulence factor of B. pertussis (17), ADP-ribosylates G ␣i proteins in mammalian cells, disrupting G protein-coupled receptor (GPCR) signaling (18,19). In adult mice, PT plays an important early role in promoting infection by inhibiting innate immune responses (20)(21)(22)(23)(24)(25).…”

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confidence: 99%

Fatal Pertussis in the Neonatal Mouse Model Is Associated with Pertussis Toxin-Mediated Pathology beyond the Airways

et al. 2017

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In infants, can cause severe disease, manifested as pronounced leukocytosis, pulmonary hypertension, and even death. The exact cause of death remains unknown, and no effective therapies for treating fulminant pertussis exist. In this study, a neonatal mouse model of critical pertussis is characterized, and a central role for pertussis toxin (PT) is described. PT promoted colonization, leukocytosis, T cell phenotypic changes, systemic pathology, and death in neonatal but not adult mice. Surprisingly, PT inhibited lung inflammatory pathology in neonates, a result which contrasts dramatically with observed PT-promoted pathology in adult mice. Infection with a PT-deficient strain induced severe pulmonary inflammation but not mortality in neonatal mice, suggesting that death in these mice was not associated with impaired lung function. Dissemination of infection beyond the lungs was also detected in neonatal mice, which may contribute to the observed systemic effects of PT. We propose that it is the systemic activity of pertussis toxin and not pulmonary pathology that promotes mortality in critical pertussis. In addition, we observed transmission of infection between neonatal mice, the first report of transmission in mice. This model will be a valuable tool to investigate causes of pertussis pathogenesis and identify potential therapies for critical pertussis.

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Fatal Pertussis in the Neonatal Mouse Model Is Associated with Pertussis Toxin-Mediated Pathology beyond the Airways

et al. 2017

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“…Pertussis toxin (PTX) in an inactivated form (PTd) functions as a major protective antigen, stimulating production of toxinneutralizing antibodies which can protect against damage caused by the toxin, but do not target the bacteria itself (301,302); however, it also demonstrates possible partial reversion back to its toxic active form (303,304), which may be responsible for the reactogenicity seen in a small percentage of vaccine recipients. It is also a secretory protein, which is only loosely associated with the cell and is therefore not an ideal target for bactericidal antibodies.…”

Section: Los-derived Oligosaccharide Glycoconjugatesmentioning

confidence: 99%

Immunomodulation as a Novel Strategy for Prevention and Treatment of Bordetella spp. Infections

2019

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Well-adapted pathogens have evolved to survive the many challenges of a robust immune response. Defending against all host antimicrobials simultaneously would be exceedingly difficult, if not impossible, so many co-evolved organisms utilize immunomodulatory tools to subvert, distract, and/or evade the host immune response. Bordetella spp. present many examples of the diversity of immunomodulators and an exceptional experimental system in which to study them. Recent advances in this experimental system suggest strategies for interventions that tweak immunity to disrupt bacterial immunomodulation, engaging more effective host immunity to better prevent and treat infections. Here we review advances in the understanding of respiratory pathogens, with special focus on Bordetella spp., and prospects for the use of immune-stimulatory interventions in the prevention and treatment of infection.

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“…Since the move to aPV in most countries in recent years, a detoxified form of PT has been a component of all of these vaccines, in recognition of its role as a protective antigen against severe disease in infants (Coutte and Locht 2015). Although most of these vaccines contain other pertussis antigens, a monocomponent detoxified PT vaccine is used in Denmark (Thierry-Carstensen et al 2013).…”

Section: Pt As a Pertussis Vaccine Component And Therapeutic Targetmentioning

confidence: 99%

Role of Major Toxin Virulence Factors in Pertussis Infection and Disease Pathogenesis

Scanlon

Skerry

Carbonetti

2019

Advances in Experimental Medicine and Biology

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Bordetella pertussis produces several toxins that affect host-pathogen interactions. Of these, the major toxins that contribute to pertussis infection and disease are pertussis toxin, adenylate cyclase toxin-hemolysin and tracheal cytotoxin. Pertussis toxin is a multi-subunit protein toxin that inhibits host G protein-coupled receptor signaling, causing a wide array of effects on the host. Adenylate cyclase toxin-hemolysin is a single polypeptide, containing an adenylate cyclase enzymatic domain coupled to a hemolysin domain, that primarily targets phagocytic cells to inhibit their antibacterial activities. Tracheal cytotoxin is a fragment of peptidoglycan released by B. pertussis that elicits damaging inflammatory responses in host cells. This chapter describes these three virulence factors of B. pertussis, summarizing background information and focusing on the role of each toxin in infection and disease pathogenesis, as well as their role in pertussis vaccination.

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Investigating Pertussis Toxin and its Impact on Vaccination

Cited by 17 publications

References 117 publications

Fatal Pertussis in the Neonatal Mouse Model Is Associated with Pertussis Toxin-Mediated Pathology beyond the Airways

Fatal Pertussis in the Neonatal Mouse Model Is Associated with Pertussis Toxin-Mediated Pathology beyond the Airways

Immunomodulation as a Novel Strategy for Prevention and Treatment of Bordetella spp. Infections

Role of Major Toxin Virulence Factors in Pertussis Infection and Disease Pathogenesis

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