Matrix Metalloproteinase 9 Production by Monocytes is Enhanced by TNF and Participates in the Pathology of Human Cutaneous Leishmaniasis: e3282

• Published in: PLoS neglected tropical diseases 2014-11, Vol.8 (11)
• Main Authors: Campos, Taís M, Passos, Sara T, Novais, Fernanda O, Beiting, Daniel P, Costa, Rúbia S, Queiroz, Adriano, Mosser, David, Scott, Phillip, Carvalho, Edgar M, Carvalho, Lucas P
• Format: Article
• Language: English
• Subjects: Cytokines; Enzymes; Infections; Pathogenesis; Pathology; Tropical diseases; Ulcers
• ISSN: 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0003282

Introduction Cutaneous leishmaniasis (CL) due to L.braziliensis infection is characterized by a strong inflammatory response with high levels of TNF and ulcer development. Less attention has been given to the role of mononuclear phagocytes to this process. Monocytes constitute a heterogeneous population subdivided into classical, intermediate and non-classical, and are known to migrate to inflammatory sites and secrete inflammatory mediators. TNF participates in the induction of matrix metalloproteinases (MMPs). MMP-9 is an enzyme that degrades basal membrane and its activity is controlled by the tissue inhibitor of metalloproteinase. Methods Mononuclear cells were obtained from ex-vivo labeling sub-populations of monocytes and MMP-9, and the frequency was determined by flow cytometry. Culture was performed during 72 hours, stimulating the cells with SLA, levels of MMP-9 and TIMP-1 in the supernatants were determined by ELISA. Results We observed that cells from CL lesions secrete high amounts of MMP-9 when compared to healthy subjects. Although MMP-9 was produced by monocytes, non-classical ones were the main source of this enzyme. We also observed that TNF produced in high level during CL contributes to MMP-9 production. Conclusions These observations emphasize the role of monocytes, TNF and MMP-9 in the pathogenesis of L. braziliensis infection.