AbstractES‐62, a protein secreted by Acanthocheilonema viteae, is anti‐inflammatory by virtue of covalently attached phosphorylcholine (PC) residues and thus a library of drug‐like small molecule analogues (SMAs) based on its PC moieties has been designed for therapeutic purposes. Two members, SMAs 11a and 12b, were previously found to suppress production of pro‐inflammatory cytokines by mouse bone marrow‐derived macrophages (BMMs) exposed to cytosine‐phosphate‐guanosine oligodeoxynucleotides (CpG), agonists for Toll‐like receptor 9. In order to explore the mechanism of action underlying such activities, an untargeted mass spectrometry‐based metabolomics screen was undertaken. Stimulation of BMMs with CpG produced significant metabolic changes relating to glycolysis and the TCA cycle but the SMAs had little impact on this. Also, the SMAs did not promote alterations in metabolites known to be associated with macrophage M1/M2 polarization. Rather, BMMs exposed to SMAs 11a or 12b prior to CpG treatment, or even alone, revealed downregulation of metabolites of creatine, a molecule whose major role is in the transport of high energy phosphate from the mitochondria to the cytosol. These data therefore provide insight into a possible mechanism of action of molecules with significant therapeutic potential that has not previously been described for parasitic worm products.

01 Nov 2021·Zhongguo xue xi chong bing fang zhi za zhi = Chinese journal of schistosomiasis control

[Role of the ES-62 protein derived from Acanthocheilonema viteae in regulation of immune dysregulation diseases: a review].

Review

Author: Xing, J Y ; Huang, T T ; Wu, P ; Hu, Q ; Yang, X D

ES-62 is a phosphorylcholine-containing, 62 kDa glycoprotein derived from the excretory-secretory product of Acanthocheilonema viteae, which is effective for the prevention and treatment of immune dysregulation diseases through triggering activation of immune cells, such as dendritic cells, mononuclear macrophages and regulatory B cells and mediating immune responses. Recently, the role of the ES-62 protein in the management of allergic, autoimmune and metabolic diseases has been paid much attention. This review summarizes the regulatory role of the ES-62 protein in immune dysregulation diseases and the underlying mechanisms, so as to provide insights into future experimental studies.

01 Oct 2021·Autoimmunity ReviewsQ1 · MEDICINE

Parasite-based interventions in systemic lupus erythematosus (SLE): A systematic review

Q1 · MEDICINE

Review

Author: Rahimi, Mohammad Taghi ; Jafari, Reza ; Mirmoeeni, Seyyedmohammadsadeq ; Jafari, Amirhossein Azari ; Keikha, Mojtaba

BACKGROUNDThe hygiene hypothesis proposed in 1989 expresses that allergic and infectious diseases are inversely related. Accordingly, it has been demonstrated that infection with some microorganisms such as parasites and helminths can provide a potential immunity and prevent the onset of some life-threatening autoimmune diseases like systemic lupus erythematosus (SLE). Therefore, in this comprehensive study, we systematically reviewed and discussed the use of live parasites or parasitic products in the treatment of mouse models of SLE.METHODSThe present systematic review was performed using the following search terms: ("systemic lupus erythematosus" OR "SLE" OR "lupus") AND ("parasite" OR "protozoa" OR "helminths" OR "worms" OR "helminth" OR "worm") in PubMed, Scopus, and Web of Science online databases. We included studies reporting the effect of any intervention using parasites or parasitic-based products on animal models of SLE, which were published until January 20th, 2021 without any language or date restrictions. For each included study, we extracted the authors' names, publication year, type of animal, number of groups, types of intervention, sample size, changes in immunologic cells, auto-Abs, cytokines, and blood cells count, urine analysis, histological analysis of kidney/spleen/liver, outcome and survival. (PROSPERO CRD42020160460).RESULTSA total of 17 eligible articles were included in this systematic review. Sixteen out of the 17 studies reported immunomodulating changes in immunologic cells, cytokines, and/or auto-Abs in mouse models of SLE after using parasitic interventions compared to not-infected or control groups. Moreover, 14 studies reported decreased level of proteinuria and/or favorable kidney, liver, or spleen histological changes.CONCLUSIONIn conclusion, we have demonstrated that parasites like Hymenolepis microstoma, TPC and ES-62 from Acanthocheilonema viteae, Plasmodium chabaudi, Schistosoma mansoni, and Toxoplasma gondii have favorable immunomodulating effects on SLE outcomes in lupus-prone mice.

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Indication	Highest Phase	Country/Location	Organization	Date
Immune System Diseases	Preclinical	GB	University of Strathclyde	-
Immune System Diseases	Preclinical	GB	University of Glasgow	-
Inflammation	Preclinical	GB	University of Strathclyde	-
Inflammation	Preclinical	GB	University of Glasgow	-

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