Role of IL-21 in host pathogenesis in experimental visceral leishmaniasis

Abstract

Visceral leishmaniasis (VL) is a major global health problem but still remains one of the neglected tropical diseases. Currently available chemotherapeutics are associated with severe toxicity and increased drug resistance. There is a need to explore for novel therapeutic strategies that could modulate host immune responses or work in synergy with chemotherapy of VL. Therefore, understanding the host immunological changes that play a vital role in disease pathology is a prerequisite for designing any interventions. We have investigated the role of IL-21 during the course of Leishmania donovani infection and after drug treatment. BALB/c mice were used to investigate the mRNA levels of IL-21 during active Leishmania donovani infection and after treatment using real time polymerase chain reaction (RT-PCR). Mice were divided in four groups i.e. Control (Group A), Infected (Group B), Uninfected treated (Group C) and Infected treated (Group D). Animals of Group C and D were treated with Amphotericin B. IL-21 mRNA levels in the spleen were estimated on days 1, 3, 7, 14, 17, 21, 28, 35, 45 and 60 post infection and also during course of treatment. We found that IL-21 mRNA levels was significantly up-regulated in the infected group with a fourfold increase at D60 p.i. (p \ 0.001) and it was decreased significantly after the treatment. Our results suggest that IL-21 mRNA is associated with pathogenesis of Leishmania donovani infection and that therapeutics designed to suppress IL-21 could provide promising antileishmanial activity.

Cytokines and splenic remodelling during Leishmania donovani infection

“…IL-27 and IL-21 have also been reported to maintain IL-10 levels during VL [49] . Consistent with these findings, IL-21 mRNA was upregulated by 4-fold even at day 60 post infection in the spleen [50] . These findings highlight the therapeutic potential for targeting IL-10 and IFN-I signalling pathways in the context of drug treatment for the purposes of improving disease outcome in VL.…”

Transcriptome Analysis Identifies Immune Markers Related to Visceral Leishmaniasis Establishment in the Experimental Model of BALB/c Mice

“…It has been proposed that IL-21 acts as a VL-promoting cytokine through the regulation and expansion of pathogenic anti-inflammatory cytokine IL-10, as evidenced by elevated IL-21 mRNA in splenic aspirate cells from patients with active disease (56), as well as in experimental models of BALB/c mice and hamsters infected with L . donovani parasite (57, 58). IL-10 is the main disease promoting cytokine in VL.…”

Unravelling the unsolved paradoxes of cytokine families in host resistance and susceptibility to Leishmania infection

“…In experimental VL, L. donovani -infected BALB/c mice have increased levels of IL-21 compared to uninfected controls suggesting a role for IL-21 in susceptibility [36] . In line with this, evidence suggests that IL-21/IL-21R signalling regulates antibody isotype switching especially IgG subclasses, IgG1 and IgA [37] , the former associated with progression of leishmaniasis [35] .…”