A secondary wave of neutrophil infiltration causes necrosis and ulceration in lesions of experimental American cutaneous leishmaniasis

• DOI: 10.1371/journal.pone.0179084
• Publication Date: 2017-06-07T17:37:12Z
• Authors: Alex G. Peniche; Diana L. Bonilla; Gloria I. Palma; Peter C. Melby; Bruno L. Travi; E. Yaneth Osorio
• Keywords: Infiltration (HVAC); Cathepsin G; Neutrophil elastase; Neutrophil Extracellular Traps; Cellular infiltration; Proteinase 3

We evaluated the importance of neutrophils in development chronic lesions caused by L. Viannia spp. using hamster as experimental model American Cutaneous Leishmaniasis (ACL). Neutrophils infiltrated lesion within first six hours post-infection. Inhibition this early infiltration a polyclonal antibody or cyclophosphamide was associated with transient parasite control but protective effect vanished when became clinically apparent. At onset (approximately 10 days p.i.), there an increased proportion both uninfected and infected macrophages, subsequently second wave (after 19 p.i.) This neutrophil necrosis ulceration (R2 = 0.75) maximum burden. Intradermal delivery N-formylmethionyl-leucyl-phenylalanine (fMLP), aimed to increase infiltration, resulted larger marked higher burden than mock treated groups (p<0.001 each). In contrast, reduced via cyclophosphamide-mediated depletion led more benign lower loads compared controls expressed significantly GM-CSF, reactive oxygen species nitric oxide those wave, suggesting that they had less efficient anti-leishmania activity. However, inflammatory cytokines expression proteases (myeloperoxidase, cathepsin G elastase) during levels reached (6h p.i.). suggests augmented secondary could contribute skin inflammation, ACL. The overall results indicate were unable clear infection model, played important role severity