Table 1.
Experimental studies and human trials of parasite-derived therapies for important autoimmune diseases.
| Autoimmune disease | Parasite | Effect | Useful component | Reference |
|---|---|---|---|---|
| Inflammatory bowel disease (IBD) | Schistosoma mansoni | S. mansoni cercaria infection attenuates DSS-induced colitis in mice. Immunization with P28GST, a unique recombinant schistosome enzyme, ameliorates intestinal inflammation by eosinophil-dependent modulation of harmful type 1 responses, representing a new immunoregulatory strategy against IBD (Driss et al., 2016). | Soluble egg antigen (SEA), soluble worm antigen (SWA), glutathione S-transferase P28GST, Sj16 | Ruyssers et al., 2009; Bodammer et al., 2011; Heylen et al., 2014a; Hasby et al., 2015; Driss et al., 2016 |
| Schistosoma japonicum | S. japonicum ova pre-treatment contributes to the relief of colitis and decreases mortality in a TNBS-induced colitis model, modulating the activity of CD4+CD25+Treg cells. | Cystatin |
Xia et al., 2011; Wang et al., 2016 |
|
| Ancylostoma caninum | Ameliorates TNBS-induced colitis in mice, decreases production of pro-inflammatory cytokines (IFN-γ and IL-17), and increases production of regulatory cytokines (IL-10 and TGF-β) in colon tissue. | Soluble antigen | Ruyssers et al., 2009 | |
| Hymenolepis diminuta | Colitis suppressed by adoptive transfer of antigen-treated dendritic cells. | Adult worm extract | Reyes et al., 2015, 2016a; Matisz et al., 2017 | |
| Anisakis | Anisakis excretory-secretory (ES) compounds have a protective effect on intestinal immunopathology. | ES products isolated from Anisakis larvae | Haarder et al., 2017 | |
| Ascaris lumbricoides | Reduces inflammation in a mouse model of DSS-induced colitis, probably by increasing the expression of anti-inflammatory cytokines (IL-10 and TGF-β) and reducing pro-inflammatory ones (IL-6 and TNF-α). | Recombinant cystatin | Coronado et al., 2017 | |
| Heligmosomoides polygyrus | Alteration of the gut microbiota is a significant contributor to the H. polygyrus-induced exacerbation of C. rodentium colitis. | Su et al., 2017 | ||
| Trichuris suis | Clinical trials using T. suis for treatment of active Crohn’s disease and ulcerative colitis showed that most of the patients experienced clinical improvement and no adverse effects. | Ova |
Summers et al., 2003, 2005a,b; Elliott and Weinstock, 2017; Su et al., 2017; |
|
| Necator americanus | Clinical trials showed that N. americanus L3 may have a therapeutic effect on Crohn’s disease, with improved CDAI in 5/9 patients at 20 weeks and 3/5 patients at 45 weeks, and mild adverse events. | Elliott and Weinstock, 2017 | ||
| Clonorchis sinensis | Reduces DSS-induced colitis by induction of IL-10 production by macrophages. | Recombinant type-1 cystatin (Csstefin-1) | Jang et al., 2011 | |
| Brugia malayi | Reduces T-cell-mediated colitis by reducing IFNr and IL-17 in the spleen, mesenteric lymph nodes, and lamina propria, and increasing IL-4 and IL-10. | Recombinant asparaginyl-tRNA synthetase (AsnRS) | Kron et al., 2013 | |
| Echinococcus granulosus | Attenuates DSS-induced colitis by reducing iNOS expression in the colon but not in the plasma | Laminated layer crude extract | Soufli et al., 2015 | |
| Rheumatoid arthritis | Schistosoma mansoni | Protective effects on the clinical and immunopathological features of rheumatoid arthritis by reducing serum IL-17 and increasing IFN-r and IL-10. Reduces collagen-induced arthritis by downregulation of the Th1 (IFN-r) response and pro-inflammatory cytokines (TNF-α and IL-17A), and upregulation of the Th2 (IL-4) response and an anti-inflammatory cytokine (IL-10). | Autoclaved S. mansoni antigen (ASMA) | Eissa et al., 2016 |
| Schistosoma japonicum | Attenuates murine collagen-induced arthritis by augmenting IL-4, IL-10, and collagen-specific IgG1, distinctly reducing IFN-r and collagen-specific IgG2a, and decreasing IL-6, IL-17, TNF-α, and RANKL. Reduces severity of complete Freund’s adjuvant-induced arthritis in a rat model by increasing production of IL-10 and IL-4 and decreasing production of IL-12p70 and IFN-r. | Recombinant SjCystatin and Sj16 | Sun et al., 2010; Song et al., 2011; Liu et al., 2016 | |
| Schistosoma japonicum | Attenuates murine collagen-induced arthritis by augmenting IL-4, IL-10, and collagen-specific IgG1, distinctly reducing IFN-r and collagen-specific IgG2a, and decreasing IL-6, IL-17, TNF-α, and RANKL. Reduces severity of complete Freund’s adjuvant-induced arthritis in a rat model by increasing production of IL-10 and IL-4 and decreasing production of IL-12p70 and IFN-r. | Recombinant SjCystatin and Sj16 | Sun et al., 2010; Song et al., 2011; Liu et al., 2016 | |
| Trichinella spiralis | Protective effects on the clinical and immunopathological features of rheumatoid arthritis by reducing serum IL-17 and increasing IFN-r and IL-10. | Autoclaved T. spiralis antigen (ATSA) | Eissa et al., 2016 | |
| Fasciola hepatica | Inhibits the symptoms of collagen-induced arthritis through Foxp3+ regulatory T cells | F. hepatica total extract | Carranza et al., 2012 | |
| Hymenoleptis diminuta | Attenuates complete Freund’s adjuvant-induced arthritis. Protection abrogated in mice lacking T and B cells or IL-4Ra or IL-10. | Shi et al., 2011 | ||
| Multiple sclerosis | Schistosoma mansoni | Alters the progression of EAE. Increases IL-4, IL-10, and TGF-β, decreases IFN-r, TNF-α, and IL-12, and changes CNS inflammation. | Ova, soluble egg antigens (SEA) | La Flamme et al., 2003; Sewell et al., 2003; Zheng et al., 2012 |
| Trichuris suis | Reduces disease severity in a multiple sclerosis model. Markedly reduces Th1 and Th17 responses. | ES products | Hansen et al., 2017 | |
| Toxascaris leonina | Inhibits remission of EAE, markedly increases the number of CD45R/B220(+)B cells, and decreases INF-r and TNF-α. | Recombinant galectin (rTl-gal) isolated from adult worms | Bing et al., 2015 | |
| Trichinella spiralis | Ameliorates EAE in mice and DA rats. Shifts the Th2 response and increases the number of Treg cells. | ES product from muscle L1 larvae (ESL1) | Gruden-Movsesijan et al., 2008, 2010; Radovic et al., 2015 | |
| Schistosoma japonicum | Attenuates EAE. Increases IL-4 and decreases IFN-r and CNS inflammation. | Soluble egg antigen (SEA) | Zheng et al., 2008 | |
| Fasciola hepatica | Attenuates EAE. Enhances anti-inflammatory cytokines (IL-33 and IL-5) and Th2 responses. Protection against EAE is independent of IL-4, IL-10, and Treg cells. | ES products (FHES) | Finlay et al., 2016 | |
| Taenia crassiceps | Suppresses EAE development. Induces a range of Th2-type cytokines, while suppressing Th1 and Th17 responses, and increases tolerogenic DC and M macrophages. | ES products (TcES) | Finlay et al., 2016 | |
| Plasmodium chabaudi | Modifies the clinical course of EAE. Decreases IL-17 and IFN-r, and increases IL-10, TGF-β1, and Treg cells. | Farias et al., 2011 | ||
| Systemic lupus erythematosus (SLE) | Plasmodium chabaudi | Ameliorates the histopathological changes in a murine model of SLE. Significantly increases plasma levels of IL-4, IL-6, IL-7, IL-12, IL-17, IFN-α, IFN-γ, TGF-β, BAFF, and APRIL and markedly increases IgG2a, IgG3, and anti-dsDNA autoantibodies. Attenuates B cell autoreactivity by modulating the CXCL12/CXCR4 axis and its downstream signals PI3K/AKT, NFκB, and Erk. | Badr et al., 2015; Abdel-Maksoud et al., 2016 | |
| Acanthocheilonema viteae | Protective effect on SLE by downregulating myeloid differentiation factor 88 (MyD88) expression by B cells and kidney cells. | ES-62 | Rodgers et al., 2015 | |
| Schistosoma mansoni | Modifies the cytokine microenvironment and alters the pathological phenotype of autoimmune nephritis. Skews the immune response to the Th2 response and increases IL-10. | Miyake et al., 2014; Savio and Coutinho-Silva, 2016 | ||
| Type 1 diabetes | Schistosoma mansoni | Ameliorates streptozotocin-induced T1D in wild-type mice via a Treg/IL-4/IL-13/IL-10-independent mechanism that may be related to augmented expression of Arg-1 and Ym1. | Savio and Coutinho-Silva, 2016 | |
| Brugia malayi | rBMALT-2 has effective immunomodulatory and anti-diabetic effects by skewing the immune response to the Th2 response. | Filarial abundant larval transcript 2 (ALT-2) | Reddy et al., 2017 | |
| Fasciola hepatica | Ameliorates SLE and modulates macrophage function. | FhHDM-1 | Reddy et al., 2017 | |
| Trichinella spiralis | Prevents diabetes in NOD mice by disrupting the pathways leading to the Th1-mediated destruction of insulin-producing beta cells. | Saunders et al., 2007 | ||
| Dirofilaria immitis | Prevents diabetes in NOD mice and increases IgE. | Imai et al., 2001 |