Resiniferatoxin modulates the Th1 immune response and protects the host during intestinal nematode infection

Abstract

In the early stage of the intestinal phase of Trichinella spiralis infection, the host triggers a Th1-type immune response with the aim of eliminating the parasite. However, this response damages the host which favours the survival of the parasite. In the search for novel pharmacological strategies that inhibit the Th1 immune response and assist the host against T. spiralis infection, a recent study showed that resiniferatoxin had anti-inflammatory activity contributed to the host in T. spiralis infection. In this study, we evaluated whether RTX modulates the host immune response through the inhibition of Th1 cytokines in the intestinal phase. In addition, it was determined whether the treatment with RTX affects the infectivity of T. spiralis-L1 and the development of the T. spiralis life cycle. Our results show that RTX decreased serum levels of IL-12, INF-γ, IL-1β, TNF-α and parasite burden on muscle tissue. It was observed that T. spiralis-L1 treated with RTX decreased their infectivity affecting the development of the T. spiralis life cycle in mouse. These results demonstrate that RTX is able to inhibit the production of Th1 cytokines, contributing to the defence against T. spiralis, which places it as a potential drug modulator of the immune response.

Primary characterization of the immune response in pigs infected with Trichinella spiralis

“…It is natural that increasing the infection dose increases ML burden due to increase of NBL. The lower RCI in the low-infective-dose group may be due to the presence of significant Th2 and Treg immune responses, which suppress the Th1 immune response and promote worm expulsion [12,20]. Meanwhile, a significant Th17 immune response in the low-infective-dose group participated in worm expulsion at the intestinal stage [26].…”

“…The aim of the Th1-type immune response is to eliminate the parasite. However, this response damages the host, which favors the survival of the parasite [20]. The Th1 type cytokine IL-12 delays worm expulsion and increases worm burden in an IFNγ-independent manner [50].…”

“…The Th1 phenotype immune response is induced during the intestinal stage and predominantly induces a Th2-type immune response during the ML phase [19]. The role of the Th1-type immune response contributes to parasites elimination [20]. Th2type immune responses may help alleviating tissue damage and strengthen tissue repair [21].…”

Cytokine Profiling Plays a Crucial Role in Activating Immune System to Clear Infectious Pathogens

“…PAMPs derived from helminth parasites induce the activation and maturation of dendritic cells [147,148], promoting the development of the Th1 immune response [149], which results in a significant increase of Th1 cytokines such as IL-12 [150][151][152], INF-γ [149][150][151][152][153], IL-1β [152,154], and TNF-α [150][151][152]155] (Figure 5). However, in recent years, several studies have shown that this immune response of Th1 type favors infection by helminth parasites.…”

Adipose Tissue and Inflammation

“…Although TNF-α, a potent pro-inflammatory cytokine [9,10] was the first cytokine discovered that is secreted by adipose tissue [11], the leptin was the first molecule with hormonal activity that is secreted by adipocytes. Since then, multiple molecules called adipokines have been discovered as factors that are secreted by adipocytes or by the stromal-vascular fraction, composed mainly by macrophages, neutrophils, lymphocytes, fibroblast, and endothelial cells.…”