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Leptospirosis is a zoonotic disease due to motile Spirochete bacteria. All vertebrates can be infected with pathogenic Leptospira species, such as Leptospira interrogans (L.i) that is responsible for the more severe forms of disease. Different mammals present various disease symptoms and susceptibility, which is puzzling and not understood. For example, rats and mice are asymptomatic renal carriers of leptospires, cattle suffer morbidity and abortions, whereas humans and hamsters can die from acute leptospirosis. Prevalence of leptospirosis is high in tropical and subtropical areas, and in low-income countries with poor sanitation, where seasonal rains and global warming favor the dissemination of leptospires via contaminated sewage. Despite its health and economic burden, leptospirosis is a reemerging neglected disease, but it is not even cited as such by the WHO.

Challenge       

The “One Health” concept recognizes that human, animal, and environment health are closely interrelated. Leptospira interrogans are the causative bacterial agent of leptospirosis, an emerging zoonotic disease affecting humans and animals, worldwide. Pathogenic leptospires present in the environment can infect a broad range of hosts and the disease may appear as an acute, even fatal infection in accidental hosts, such as humans or livestock, or progress into a chronic, mainly asymptomatic infection in its natural hosts, such as mice and rats. In cattle, leptospirosis is responsible for high economic losses due to reduction in both, dairy and beef industry, and to high abortion rates.

To improve on this, it is imperative to understand the innate immune responses elicited in different hosts, as this is key to understand the diverse disease outcomes seen in the different hosts. Many immunological experiments conducted in mice have allowed the understanding of some aspects of the immune responses during leptospirosis. However, our recent work has shown clear differences in the response seen in other mammalian hosts such as human and cattle.

Solution      

In this proposal we aim to apply a comparative analysis of the innate immune responses elicited by macrophages from divergent hosts such as bovines, pigs, mice, hamsters, and humans upon infection with various zoonotic Leptospira strains that were responsible for distinct outcomes of disease. The goal of this project will be to understand differential and specific immunological processes and pathways. More specifically, we aim to compare some Toll-like receptors recognition of membrane components of leptospires, using structural, biochemical, genomic, immunological, high content screening confocal microscopy and computational modelling approaches.  

Impact      

 This project should help to better understand the innate immune mechanisms driving host specificities of leptospirosis, and accordingly tailor host directed intervention strategies.

People

Dr Natalie Werling

Partners      

Dr Catherine Wertz, Pasteur Institute
Dr Karina Caimi, INTA

Publications