Protection mediated by chemokine CXCL10 in BALB/c mice infected by Leishmania infantum

Abstract

BACKGROUND Visceral leishmaniasis (VL) caused by Leishmania infantum is characterised by the loss of the ability of the host to generate an effective immune response. Chemokines have a direct involvement in the pathogenesis of leishmaniasis, causing a rapid change in the expression of these molecules during infection by Leishmania.OBJECTIVES Herein, it was investigated the role of CXCL10 in controlling infection by L. infantum.METHODS RAW 264.7 macrophages were infected with L. infantum in vitro and treated or not with CXCL10 (25, 50 and 100 ng/mL). Parasite load, as well as nitric oxide (NO), IL-4 and IL-10 production were assessed at 24 and 48 h after infection. In vivo, BALB/c mice were infected and treated or not with CXCL10 (5 μg/kg) at one, three and seven days of infection. Parasite load, IFN-g, IL-4, TGF-β and IL-10 were evaluated one, seven and 23 days post treatment.FINDINGS In vitro, CXCL10 reduced parasitic load, not dependent on NO, and inhibited IL-10 and IL-4 secretion. In vivo, CXCL10 was able to reduce the parasite load in both liver and spleen, four weeks after infection, representing a higher decrease in the number of parasites in these organs, also induced IFN-γ at day 23 after treatment, correlating with the decrease in parasite load, and reduced IL-10 and TGF-β.MAIN CONCLUSIONS This study suggests a partial protective role of CXCL10 against L. infantum, mediated by IFN-g, not dependent on NO, and with suppression of IL-10 and TGF-β. These data may provide information for the development of new approaches for future therapeutic interventions for VL.

Chlorogenic acid acts upon Leishmania donovani arresting cell cycle and modulating cytokines and nitric oxide in vitro

“…Another study with L. major ‐infected RAW.264.7 cells showed increased production of TNF and IL‐12 at mRNA level, when stimulated with IFN‐γ + LPS 40 . Antileishmanial activity of different compounds and therefore NO release from RAW264.7 cells is also reported 38,41 . These reports are supportive of the fact that the modulation of cytokine production by the RAW264.7 cells observed in our study could essentially steer the amastigote clearance.…”

“…Our observation of reduction of IL‐10 and increase in IL‐12, TNF and NO in the L. donovani ‐infected RAW264.7 cells upon CGA treatment may be a consequence of restoration of the impaired macrophage activity after parasite clearance. Induction of IL‐10 from RAW264.7 cells upon infection of L. donovani infection is reported both at mRNA and protein level 36‐38 . Inhibition of IL‐12 production from RAW264.7 cells upon Leishmania infection is also reported both at mRNA and protein level 37,39 .…”

T cell suppression in the bone marrow of visceral leishmaniasis patients: impact of parasite load

“…However, the contribution of a similar pathway may not be inferred for other pathological sites of visceral leishmaniasis due to differences in the architectural and immune milieu in spleen, liver and lymph nodes. Suppression of the host T cell response has also been well documented in L. infantum infection [2,3,24]. Considering the similarity of the immune response, we envisage that the parasite burden may also suppress the T cell response during L. infantum infection.…”

Integrated multivariate analysis of transcriptomic data reveals immunological mechanisms in mice afterLeishmania infantuminfection

“…CXCL10 has been studied as a treatment in BALB/c mice infected by L. infantum, since there is evidence that CXCL10-treatment reduces IL-10 + Treg cell populations (CD4 + CD25 + Foxp3 + and Tr1) and induces morphological changes in the spleen (28). This chemokine also induces a reduction in parasite burden in the spleen and a decrease in IL-10 and TGF-β production in L. infantum-infected BALB/c mice (29).…”