Invasive Salmonella infections in animal models and man: castles of cards, roundabouts, vaccines and disease

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• Dr Piero Mastroeni, Department of Veterinary Medicine, University of Cambridge
• Wednesday 11 November 2015, 16:00-17:00
• Lecture Theatre 2, Department of Veterinary Medicine.

If you have a question about this talk, please contact Fiona Roby.

The principle forms of invasive Salmonella infections, typhoid fever and invasive nontyphoidal Salmonella disease (iNTS), are both characterized by intracellular growth and extracellular systemic spread of bacteria belonging to different serovars of Salmonella enterica.

Animal models have provided many insights into those host-pathogen relationships that control invasive Salmonella infections. Immunological or genetic manipulations of B- and T-cell mediated immunity, signaling pathways, cytokine networks and phagocyte effector functions modulate host resistance/susceptibility and have provided solid information on which immunological effectors control and eliminate the disease. These models have also enabled us to test different classes of vaccines and determine which ones are likely to induce the highest level of protection in other animal species and in humans.

The higher incidence of invasive Salmonella disease in patients with genetic immunodeficiencies, individuals carrying specific immune gene alleles and patients with comorbidities (e.g. malaria, severe anaemia, HIV ), indicates common resistance/susceptibility traits between mice and humans. iNTS and typhoid fever are often inferred to be immunologically similar. It would therefore be reasonable to assume that the determinants of resistance/susceptibility to these diseases are similar and require invocation of humoral and cellular immunity. However, evidence from host susceptibility and risk factor associations provides a far more complex scenario.

The presence of comorbidities in endemic area poses serious challenges to disease prevention by undermining those element of the innate immune response that are the foundations upon which vaccines build resistance. There are currently large gaps in our knowledge of the mechanisms that control Salmonella infections is humans and we still do not fully understand of how comorbidities, alone or in combination, impair immunity.

A major challenge ahead is to link risk factors/comorbidities with specific immunological/functional defects that determine increased susceptibility to infections in endemic areas. This will provide a rational pathway to develop approaches and tools to restore such defects in individuals with high risk of contracting disease.

This talk is part of the Departmental Seminar Programme, Department of Veterinary Medicine series.

This talk is included in these lists:

• All Talks (aka the CURE list)
• Cambridge Immunology
• Cambridge Infectious Disease
• Cambridge Infectious Diseases
• Departmental Seminar Programme, Department of Veterinary Medicine
• Lecture Theatre 2, Department of Veterinary Medicine
• Vet School Seminars

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