Tissue damage and immunity in cutaneous leishmaniasis

Abstract

Cutaneous leishmaniasis (CL) is caused by parasitic infection of dermal macrophages resulting in intense immune-mediated tissue inflammation and skin ulceration. The severity of the disease is dependent on parasite species as well as the immune responses evoked by the host. Most cases of CL heal spontaneously. In rare cases, the ulcer/s become chronic, and some Leishmania species may induce mucosal leishmaniasis (MCL) leading to severe tissue damage. Due to difficulties in obtaining skin tissue, most human studies of CL have been limited to the analysis of peripheral blood. While systemic responses may be good correlates of immunity, tissue damage and local immune responses at the site of infection is seldom reflected in alterations in the peripheral blood. In this review, we discuss the different forms of CL focusing on the in situ responses in established disease and the mechanisms involved in pathology and healing of Leishmania infection. Great effort has been put into animal models dissecting the immune events behind the evolution of disease, tissue pathology and parasite control. These models of genetically engineered, immune deficient mice or mice given therapy prior to onset of overt disease poorly reflect the clinical situation, where patients seek treatment once infection is well established. Models of established disease are needed to address the clinical challenge of identifying new therapeutic targets in treatment CL. Through understanding immune deviations during CL potential benefits and risks of emerging biological drugs in leishmaniasis can be addressed.

ThreeLeishmania/L.species –L. infantum,L. major,L. tropica– as causative agents of mucosal leishmaniasis in Iran

“…While spontaneous healing happens in CL, ML leads to scarring and disfigurement and VL is life threatening. 12 Mucosal leishmaniasis usually appears as mucosal ulcerations in the cheek, lips, soft palate, hard palate, tongue, tonsils, and larynx; however, it can affect other sites too. 13 There was diversity in the clinical features of all patients.…”

Real-Time PCR Assay for Detection and Quantification of Leishmania (Viannia) Organisms in Skin and Mucosal Lesions: Exploratory Study of Parasite Load and Clinical Parameters

“…On the one hand, this suggests that Leishmania might alter local tissue homeostasis, promoting tissue damage. On the other hand, some reports show that the immune system response, rather than the parasites per se, causes ulceration and tissue destruction in ATL (33,34).…”

Assessment of β-lapachone loaded in lecithin-chitosan nanoparticles for the topical treatment of cutaneous leishmaniasis in L. major infected BALB/c mice

“…Unlike humans, where ulcerative CL are associated with low infectious loads and non-ulcerative lesions with impaired parasite clearance, the BALB/c murine CL model is always associated with widespread tissue destruction and uncontrolled parasite replication provoked by persistence of Th2 cells and IL-10, resulting in chronic tissue remodelling with necrosis and fibrosis. Thus, in BALB/c mice the size of the lesion may reflect the parasite burden as well as the degree of inflammation caused by the host immune response to the parasite [39]. In our work, the immunohistopatology of the lesions showed that, after the treatment, the tissue surrounding the ulcers, which presented epidermal hyperkeratosis, and massive infiltration of infected macrophages were similar ( Figures 4A and 4E).…”