Concerted Activity of IgG1 Antibodies and IL-4/IL-25-Dependent Effector Cells Trap Helminth Larvae in the Tissues following Vaccination with Defined Secreted Antigens, Providing Sterile Immunity to Challenge Infection

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Despite the high prevalence of gastrointestinal helminth parasites in human and animal populations throughout the world, no vaccines are yet available and we lack understanding of how anti-parasite protective immunity may operate effectively. We have used a model system with a natural mouse nematode parasite, Heligmosomoides polygyrus, which establishes long-term chronic infection in laboratory mice through the secretion of immunosuppressive molecules. Immunization of mice with as few as 3 secreted proteins, collected from parasites in vitro, confers complete immunity to challenge infection. We show here that immunity requires specific IgG1 antibodies directed to the secreted products, acting together with innate myeloid cells that require activation through the canonical Type 2 cytokine receptor, IL-4Rα, as well as through a pathway not previously known to be involved in effector mechanisms, IL-25. These myeloid cells act to trap and envelop helminth larvae while in the submucosal tissues of the small intestine, massing in large numbers and preventing their maturation and exit into the gut lumen. Thus the combined effects of specific antibodies from the adaptive immune system, and Type 2 cytokine activation of the innate immune system, co-operate to ensure elimination of the helminth parasite.

Vyšlo v časopise: Concerted Activity of IgG1 Antibodies and IL-4/IL-25-Dependent Effector Cells Trap Helminth Larvae in the Tissues following Vaccination with Defined Secreted Antigens, Providing Sterile Immunity to Challenge Infection. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004676
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004676

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