Type-I interferons promote innate immune tolerance in macrophages exposed to Mycobacterium ulcerans vesicles.

Buruli ulcer is a chronic infectious disease caused by Mycobacterium ulcerans. The pathogen persistence in host skin is associated with the development of ulcerative and necrotic lesions leading to permanent disabilities in most patients. However, few of diagnosed cases are thought to resolve through an unknown self-healing process. Using in vitro and in vivo mouse models and M. ulcerans purified vesicles and mycolactone, we showed that the development of an innate immune tolerance was only specific to macrophages from mice able to heal spontaneously. This tolerance mechanism depends on a type I interferon response and can be induced by interferon beta. A type I interferon signature was further detected during in vivo infection in mice as well as in skin samples from patients under antibiotics regiment. Our results indicate that type I interferon-related genes expressed in macrophages may promote tolerance and healing during infection with skin damaging pathogen.

A combined field study of Buruli ulcer disease in southeast Benin proposing preventive strategies based on epidemiological, geographic, behavioural and environmental analyses.

Buruli ulcer is a neglected tropical disease caused by M. ulcerans, an environmental mycobacterium. This cutaneous infectious disease affects populations with poor access to sanitation, safe water and healthcare living in rural areas of West and Central Africa. Stagnant open bodies of surface water and slow-running streams are the only risk factor identified in Africa, and there is no human-to-human transmission. Appropriate and effective prevention strategies are required for populations living in endemic areas. Based on a multidisciplinary approach in an area in which Buruli ulcer is endemic in South Benin, we investigated the link between all human-environment interactions relating to unprotected water and behaviors associated with Buruli ulcer risk likely to affect incidence rates. We characterised the sources of water as well as water bodies and streams used by communities, by conducting a prospective case-control study directly coupled with geographic field observations, spatial analysis, and the detection of M. ulcerans in the environment. A full list of the free surface waters used for domestic activities was generated for a set of 34 villages, and several types of human behaviour associated with a higher risk of transmission were identified: (i) prolonged walking in water to reach cultivated fields, (ii) collecting water, (iii) and swimming. Combining the results of the different analyses identified the risk factor most strongly associated with Buruli ulcer was the frequency of contact with unprotected and natural water, particularly in regularly flooded or irrigated lowlands. We confirm that the use of clean water from drilled wells confers protection against Buruli ulcer. These specific and refined results provide a broader scope for the design of an appropriate preventive strategy including certain practices or infrastructures observed during our field investigations. This strategy could be improved by the addition of knowledge about irrigation practices and agricultural work in low-lying areas.