Details

Autor(en) / Beteiligte

• White, Madeleine P J
• Johnston, Chris J C
• Grainger, John R
• Konkel, Joanne E
• O'Connor, Richard A
• Anderton, Stephen M
• Maizels, Rick M

Titel

The Helminth Parasite Heligmosomoides polygyrus Attenuates EAE in an IL-4Rα-Dependent Manner

Ist Teil von

• Frontiers in immunology, 2020-09, Vol.11, p.1830-1830

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Helminth parasites are effective in biasing Th2 immunity and inducing regulatory pathways that minimize excessive inflammation within their hosts, thus allowing chronic infection to occur whilst also suppressing bystander atopic or autoimmune diseases. Multiple sclerosis (MS) is a severe autoimmune disease characterized by inflammatory lesions within the central nervous system; there are very limited therapeutic options for the progressive forms of the disease and none are curative. Here, we used the experimental autoimmune encephalomyelitis (EAE) model to examine if the intestinal helminth and its excretory/secretory products (HES) are able to suppress inflammatory disease. Mice infected with at the time of immunization with the peptide used to induce EAE (myelin-oligodendrocyte glycoprotein, pMOG), showed a delay in the onset and peak severity of EAE disease, however, treatment with HES only showed a marginal delay in disease onset. Mice that received 4 weeks prior to EAE induction were also not significantly protected. secretes a known TGF-β mimic ( TGM) and simultaneous infection with pMOG immunization led to a significant expansion of Tregs; however, administering the recombinant TGM to EAE mice failed to replicate the EAE protection seen during infection, indicating that this may not be central to the disease protecting mechanism. Mice infected with also showed a systemic Th2 biasing, and restimulating splenocytes with pMOG showed release of pMOG-specific IL-4 as well as suppression of inflammatory IL-17A. Notably, a Th2-skewed response was found only in mice infected with at the time of EAE induction and not those with a chronic infection. Furthermore, failed to protect against disease in IL-4Rα mice. Together these results indicate that the EAE disease protective mechanism of is likely to be predominantly Th2 deviation, and further highlights Th2-biasing as a future therapeutic strategy for MS.