The disease is usually characterized by mild lesions that self-heal within 4–10 months although with tell-tail scarring (referred to as healed individuals), but in some cases, lesions can remain active for more Ferroptosis inhibitor clinical trial than 2 years (referred to as nonhealing individuals) (2). Leishmania can interact and infect a number of different cell types, with monocytes/macrophages being the most important. However, in the very earliest phase of infection, neutrophils are believed to serve as an intermediate host cell (3,4). The parasite has, furthermore, been suggested to use apoptotic neutrophils

as a ‘Trojan horse’ to enter macrophage as its final host (4). This initial interaction between neutrophil and parasite is likely to impact the outcome of infection. Better understanding regarding how neutrophils can be influenced by parasite or parasite products may, thus, aid in developing new tools to control leishmaniasis. The role of neutrophils has been investigated in mouse models of both visceral (VL) and CL, but there are few reports on their role in human disease (5). Both human and mouse studies have shown that neutrophils produce a number of cytokines after infection with L. major both in vitro and in vivo (3,4,6) including, TNF-α, TGF-β and IL-8, important in initiating an immune response. In vitro studies showed that co-incubation of human neutrophils with L. major Saracatinib in vitro induces IL-8 secretion

(3). Because neutrophils are also the primary target cell of IL-8, the Leishmania-induced production of IL-8 accelerates the recruitment of other neutrophils to the site of infection and facilitates uptake of the parasite

(7). The role of neutrophils mediated by TGF-β secretion in L. major infections is currently being investigated. Studies on murine models of leishmaniasis have shown that TGF-β secreted by neutrophils counteracts IL-12-mediated effects on T helper cell (Th) differentiation (8,9). Less virulent disease associated with the development of a Th1 pattern occurs in animals treated with a monoclonal antibody (mAb) against TGF-β, while more virulent disease occurs in animals given TGF-β (10). In addition, in vitro experiments indicated Dipeptidyl peptidase that induction of TGF-β production by human neutrophils results in the persistence of intracellular parasite whereas release of TNF-α contributes to elimination of intracellular parasite by neutrophils (6). Furthermore, cutaneous lesions caused by Leishmania braziliensis infection mostly heal rapidly, but the uncontrolled gelatinase activity may result in intense tissue degradation and poorly healing wounds. There is an association between gelatinase activity and increased numbers of cells making IFN-γ, IL-10 and TGF-β in lesions from poor responders. This study concluded that the immune response profile may be ultimately influence the persistence or cure of CL lesions activity (11).