Antigen-triggered interferon-γ and interleukin-10 pattern in cured mucosal leishmaniasis patients is shaped during the active phase of disease

Abstract

An exacerbated type 1 response to leishmanial antigens is the basis of tissue destruction observed in mucosal leishmaniasis (ML). After therapy, a persistent production of high levels of inflammatory cytokines can confer a poor prognosis. Herein we investigated whether the clinical conditions defined during the active phase of ML affect the magnitude of long-term anti-Leishmania immune response. Twenty clinically cured ML cases were studied. Peripheral blood mononuclear cells (PBMC) were cultured with L. braziliensis antigens (Lb-Ag), Toxoplasma gondii antigens (Tg-Ag), concanavalin-A (Con-A) or medium alone, and the lymphocyte proliferative response and cytokine secretion were quantified. Medical records were reviewed for Montenegro skin test (MST) during diagnosis, duration of ML disease or time elapsed after clinical cure. The duration of disease was correlated positively with MST (r = 0·61). Lb-Ag induced interferon (IFN)-γ was correlated positively with duration of illness (r = 0·69) as well as the frequency of secreting cells [enzyme-linked immunospot (ELISPOT)] assay. No association was observed for Tg-Ag or Con-A. Disease duration was correlated negatively with interleukin (IL)-10 production (r = −0·76). Moreover, a negative correlation between length of time after clinical cure and TNF levels (r = −0·94) or the IFN-γ : IL-10 ratio (r = −0·89) were also seen. We suggest that the magnitude of the IFN-γ inflammatory response triggered by ML can be driven by the time of leishmanial antigens exposition during the active phase of the disease. This pattern could persist even long-term after cure. However, despite IFN-γ levels, the decrease of the TNF and IFN-γ : IL-10 ratio reflects the control of proinflammatory responses achieved by cure of ML, possibly preventing disease relapses.

Correlation between Central Memory T Cell Expression and Proinflammatory Cytokine Production with Clinical Presentation of Multibacillary Leprosy Relapse

“…Our results show that the pro-inflammatory pattern of majority production of IL-1β, IL-6, and TNF in our relapsed patients remains, although at lower levels, in the cured group. Similar results were also observed in a recent study using the same standard ratio between production of pro-and anti-inflammatory cytokines in patients with mucosal leishmaniasis and individuals post leishmaniasis treatment [ 38 ].…”

The Presence of Leishmania braziliensis DNA in the Nasal Mucosa of Cutaneous Leishmaniasis Patients and the Search for Possible Clinical and Immunological Patterns of Disease Progression: A Cross Sectional Study

“…The delayed development of a protective immune response may facilitate parasite dissemination, and chronic systemic exposure to Leishmania antigens could in turn lead to the exacerbated inflammatory immune response associated with mucosal disease. This idea is in accordance with the finding that in cured ML patients, the duration of active disease is positively associated with antigen-induced production of IFN-g but negatively associated with IL-10 production (Nogueira et al, 2014).…”

The Immunology of a Healing Response in Cutaneous Leishmaniasis Treated with Localized Heat or Systemic Antimonial Therapy

“…In fact, a decrease in IFN-γ, IL-5 and TNF-α in both groups was seen at day 28 post treatment with meglumine antimoniate in a previous study [ 49 ]. These results indicate that proinflammatory responses were progressively downmodulated after therapy and that the cytokine profile produced after cure is shaped during the active phase of disease [ 50 ].…”