Adipocytes and inflammation in the cutaneous leishmaniasis outcome

Summary Leishmania braziliensis infection may cause a high spectrum of clinical manifestation, including the more prevalent form, cutaneous leishmaniasis (CL). Inflammatory response is a hallmark of CL and high levels of TNF, IL-1b, and cytotoxicity are associated with skin ulcer development in these individuals. Our preliminary data show that obese CL patients have more severe disease, longer time to heal and high levels of circulating leptin. We will characterize the inflammatory infiltrate observed in the adipose tissue from obese CL patients and determine the role of adipokines in deleterious inflammation in these individuals. Lipid profiles may vary across individuals, and they may be pro-inflammatory or contribute to the healing process. Here we will investigate the lipid profile of obese patients and seek correlation with therapeutic failure in CL. Finally, we will investigate whether lipids associated with tissue healing can reprogram macrophages to a non-inflammatory / tissue repair phenotype. We hypothesize that increased levels of leptin and a particular lipid profile enhance the inflammatory response, leading to poor outcome in obese CL individuals. The overall objective of this proposal is to determine how adipose tissue integrates with the inflammatory response, influencing the severity of CL caused by Leishmania braziliensis, and consequently increasing the rate of therapeutic failure of CL patients.