Status of IL‐4 and IL‐10 driven markers in experimental models of Visceral Leishmaniasis

Abstract

Aim Leishmania donovani, the causative agent for visceral leishmaniasis (VL), modulates host monocytes/macrophages to ensure its survival. However, knowledge regarding the host‐parasite interactions underpinning the disease remains limited. As disease progression is associated with polarization of monocytes/macrophages towards M2, which is regulated by cytokines IL‐4/IL‐13 and IL‐10, this study evaluated the status of key IL‐4‐ and IL‐10 driven markers in experimental models of VL, as also evaluated their correlation, if any, with parasite load. Methods In liver and splenic tissues from L donovani–infected hamsters and BALB/c mice, the parasite burden was determined along with mRNA expression of IL‐4–driven markers, that is CD206, Arginase‐I, CCL17, CCL22, PPAR‐γ, STAT6, KLF4, FIZZ1 and YM1 along with IL‐10–driven markers, CXCL13, IL‐10, TGF‐β, VDR, CCR2 and CYP27A1. Results The mRNA expression of IL‐4‐ and IL‐10–driven markers was enhanced in both models, but only in the hamster model, the splenic tissues demonstrated a positive correlation between all the IL‐10–driven markers and parasite load. Conclusions Contrary to human VL, both models demonstrated an increased expression of IL‐4‐ and IL‐10–driven markers.

Heterologous vaccine therapy associated with half course of Miltefosine promote activation of the proinflammatory response with control of splenic parasitism in a hamster model of visceral leishmaniasis

“…In fact, we have elucidated a strong positive correlation between interleukin-10 production and parasitic load, that is, there was no control of tissue parasitism in those animals whose IL-10 levels were high. Similarly, studies elucidated that spleen from hamsters infected presented a gradual increase in interleukin-10 ( Melby et al, 1998 ; Moulik et al, 2021 ).…”

Immunochemotherapy for visceral leishmaniasis: combinatorial action of Miltefosine plus LBSapMPL vaccine improves adaptative Th1 immune response with control of splenic parasitism in experimental hamster model

“…Our data corroborate with these concepts, whereas we observed a high spleen parasitism accompanied by lower percentage of IFN- γ and increased levels of IL-10 in infected and untreated hamsters (IA group) (Figs 2, 4 and Table 1). Similarly, other studies also showed the growth of IL-10 expression in hamsters infected (Medina-Colorado et al ., 2017; Moulik et al ., 2021). Beyond that, a strong positive correlation was found between the reduction of the splenic parasite burden and T-CD4 + IL-10 + lymphocytes levels reduced in LBSapMPL and Milt-LBSapMPL groups (Table 1).…”

T Lymphocyte Exhaustion During Human and Experimental Visceral Leishmaniasis

“…Another cytokine that plays an important suppressive role in VL is IL-10, and its role in the progression of visceral disease is already well established in both murine and human models. High levels of IL-10 are associated with a higher parasite load and are related to the development of the most severe form of disease ( 61 , 133 , 134 ). Both BALB/c and C57BL/6 mice lacking IL-10 due to either gene deletion or blockade using specific antibodies are resistant to Leishmania and do not develop the clinical manifestations of the disease ( 135 – 137 ).…”