Somatostatin Negatively Regulates Parasite Burden and Granulomatous Responses in Cysticercosis

Abstract

Cysticercosis is an infection of tissues with the larval cysts of the cestode, Taenia solium. While live parasites elicit little or no inflammation, dying parasites initiate a granulomatous reaction presenting as painful muscle nodules or seizures when cysts are located in the brain. We previously showed in the T. crassiceps murine model of cysticercosis that substance P (SP), a neuropeptide, was detected in early granulomas and was responsible for promoting granuloma formation, while somatostatin (SOM), another neuropeptide and immunomodulatory hormone, was detected in late granulomas; SOM's contribution to granuloma formation was not examined. In the current studies, we used somatostatin knockout (SOM−/−) mice to examine the hypothesis that SOM downmodulates granulomatous inflammation in cysticercosis, thereby promoting parasite growth. Our results demonstrated that parasite burden was reduced 5.9-fold in SOM−/− mice compared to WT mice (P < 0.05). This reduction in parasite burden in SOM−/− mice was accompanied by a 95% increase in size of their granulomas (P < 0.05), which contained a 1.5-fold increase in levels of IFN-γ and a 26-fold decrease in levels of IL-1β (P < 0.05 for both) compared to granulomas from WT mice. Thus, SOM regulates both parasite burden and granulomatous inflammation perhaps through modulating granuloma production of IFN-γ and IL-1β.

Regulation of immunity by Taeniids: lessons from animal models and in vitro studies

“…Thus, maybe Substance P can be associated with cysticerci destruction, whereas somatostatin with susceptibility or inhibition of granuloma formation. Indeed, a recent study has demonstrated that somatostatin knockout mice harboured lower parasite burdens associated with increased granuloma formation together with greater levels of IFN‐γ , remarking the importance of an early inflammatory response as well as granuloma formation to eliminate this parasite. The study of these interactions between neuropeptides and granuloma formation or susceptibility in Echinococcosis is an area of opportunity to deeper research.…”

Cerebrospinal fluid inflammatory cytokine profiles of patients with neurotropic parasitic infections

“…Regulation of cytokines by targeted immunomodulatory therapies may be a better option to prevent complications associated with GAE, CT, and NCC. Several molecules, namely, monoclonal antibodies (anti-TNFa inhibitor, etanercept), somatostatin analogues, nonspecific MMP inhibitor (doxycycline), aptamers, and Inonotus obliquus polysaccharide showed promise in experimental systems in the control of parasitic inflammatory responses (Khumbatta et al, 2014;Boshtam et al, 2017;Mahanty et al, 2017;Yan et al, 2021). Interestingly, patients who respond to anti-helminthic drugs show upregulation of several genes involved in pro-and anti-inflammatory and immunomodulatory functions, indicating that a pro-inflammatory environment is related to treatment responsiveness and some of them may have a role in neuroprotection (John et al, 2008;Cárdenas et al, 2014;Arce-Sillas et al, 2018).…”