Distinct plasma chemokines and cytokines signatures in Leishmania guyanensis-infected patients with cutaneous leishmaniasis

Abstract

The immunopathology associated with Leishmaniasis is a consequence of inflammation. Upon infection with Leishmania, the type of host-immune response is determinant for the clinical manifestations that can lead to either self-healing or chronic disease. Multiple pathways may determine disease severity. A comparison of systemic immune profiles in patients with cutaneous leishmaniasis caused by L. guyanensis and healthy individuals with the same socio-epidemiological characteristics coming from the same endemic areas as the patients is performed to identify particular immune profile and pathways associated with the progression of disease development. Twenty-seven plasma soluble circulating factors were evaluated between the groups by univariate and multivariate analysis. The following biomarkers pairs IL-17/IL-9 (ρ=0,829), IL-17/IL-12 (ρ=0,786), IL-6/IL-1ra (ρ=0,785), IL-6/IL-12 (ρ=0,780), IL-1β/G-CSF (ρ=0,758) and IL-17/MIP-1β (ρ=0,754) showed the highest correlation mean among the patient while only INF-γ/IL-4 (ρ=0.740), 17/MIP-1β (ρ=0,712) and IL-17/IL-9 (ρ=0,707) exhibited positive correlation among the control group. The cytokine IL-17 and IL1β presented the greater number of positive pair correlation among the patients. The linear combinations of biomarkers displayed IP-10, IL-2 and RANTES as the variables with the higher discriminatory activity in the patient group compared to PDGF, IL-1ra and eotaxin among the control subjects. IP-10, IL-2, IL-1β, RANTES and IL-17 seem to be predictive value of progression to the development of disease among the Lg-infected individuals.

Parasite genetic variation and systemic immune responses are not associated with different clinical presentations of cutaneous leishmaniasis caused by Leishmania aethiopica

“…This is in contradiction to different studies, e.g. Castellano et al (56), Espir et al (57) and de Mesquita et al (26) that showed high levels of these cytokines during active CL. These differences might be due to differences in infecting parasites, in the number of patients tested and importantly, to differences in clinical characteristics of the CL patients.…”

“…These differences might be due to differences in infecting parasites, in the number of patients tested and importantly, to differences in clinical characteristics of the CL patients. In most cases, CL patients from studies such as (26, 52, 56, 57) present with a variety of different ages. Often, the CL cohorts are not characterised in detail, with no information about their BMI, duration of illness or number of lesions.…”

“…In contrast to the experimental mouse model of CL (22–24), there are no clearly polarised Th1 and Th2 responses in patients with different clinical manifestations of CL, but a mixed production of cytokines: antigen-specific stimulation of peripheral blood mononuclear cells (PBMCs) from CL patients resulted in production of both Interferon (IFN)ψ and Interleukin (IL)-4 during the active phase of the disease, but mainly IFNψ and low IL-4 after healing (25). There were also increased levels of Th1 type cytokines, such as IFNψ, IL-2 and Tumor Necrosis Factor (TNF)α; and Th2 type cytokines, such as IL-4, IL-5 and IL-13; as well as the regulatory cytokine IL-10 in the plasma of L. guyanensis -infected CL patients (26). In patients with mucosal leishmaniasis (ML), the antigen-specific production of IFNψ and IL-5 was higher as compared to patients with CL; and the detection of IL-4 was low and only present in some ML patients (27).…”

Variants of CARD8 in Leishmania guyanensis-cutaneous leishmaniasis and influence of the variants genotypes on circulating plasma cytokines IL-1β, TNFα and IL-8

“…Unfortunately, our Kit for cytokine assay did not include IL- PLOS NEGLECTED TROPICAL DISEASES 18. We have previously shown that the plasma levels of IL-1β, TNFα, and IL-8 were higher among the patients with CL than HC [34]. Analysis of variance between plasma circulating levels of IL-1β, TNFα and IL-8 and the genotypes of either the rs73944113 C>T or rs2043211A>T did not reveal any significant correlations shown in S1 and S2 Figs, respectively. Variance analysis between genotypes of rs2288877 and rs2288876 and plasma circulating levels of IL-1β, TNFα, and IL-8 showed a significant correlation with only IL-8 S3 and S4 Figs, respectively.…”

“…Unfortunately, our Kit for cytokine assay did not include IL-18. We have previously shown that the plasma levels of IL-1β, TNFα, and IL-8 were higher among the patients with CL than HC [ 34 ]. Analysis of variance between plasma circulating levels of IL-1β, TNFα and IL-8 and the genotypes of either the rs73944113 C>T or rs2043211A>T did not reveal any significant correlations shown in S1 and S2 Figs, respectively.…”