OX40 interactions in gastrointestinal nematode infection

Area of Science:

• Immunology
• Parasitology
• Gastroenterology

Background:

• Immune expulsion of gastrointestinal nematodes typically involves T helper type 2 (Th2) responses.
• The precise mechanisms driving parasite expulsion and the role of intestinal inflammation remain unclear.
• Interleukin-4 (IL-4) controls intestinal inflammation, but its necessity for parasite expulsion is debated.
• OX40-OX40 ligand (L) signaling is crucial for Th2 responses and implicated in intestinal inflammatory diseases.

Purpose of the Study:

• To investigate the impact of OX40 and OX40L fusion protein treatment on Th2 responses and enteropathy.
• To elucidate the role of OX40-OX40L interactions in protective immunity against Trichinella spiralis infection.

Main Methods:

• Mice infected with Trichinella spiralis were treated with OX40-Ig blocking or OX40L-Ig activating fusion proteins.
• Parasite expulsion, mastocytosis, Th2 cytokine levels, and intestinal pathology (villus atrophy, crypt hyperplasia) were assessed.

Main Results:

• OX40-Ig blocking fusion protein treatment enhanced parasite expulsion and mastocytosis without altering Th2 cytokine levels.
• This blockade also delayed the development of villus atrophy and crypt hyperplasia.
• OX40L-Ig activating fusion protein treatment significantly increased Th2 cytokines but did not affect parasite expulsion or enteropathy.

Conclusions:

• OX40 ligation alone potentiates Th2 responses but does not enhance host protective immunity against Trichinella spiralis.
• Blocking the OX40-OX40L interaction promotes host protection and parasite expulsion independently of elevated Th2 cytokine production.
• Targeting the OX40-OX40L pathway offers a potential strategy for managing helminth infections and associated intestinal pathology.