Research ArticleALLERGY

Hookworm recombinant protein promotes regulatory T cell responses that suppress experimental asthma

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Science Translational Medicine  26 Oct 2016:
Vol. 8, Issue 362, pp. 362ra143
DOI: 10.1126/scitranslmed.aaf8807

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Airway allergy alleviated by hookworm protein

One reason for allergy prevalence in the developed world may be a lack of exposure to parasites, which can influence immune development and function. Because administering live parasites to people might pose safety issues, Navarro et al. tested the ability of the hookworm protein AIP-2 to treat airway allergic sensitization. Administration of AIP-2 could prevent or treat asthma symptoms in a mouse model, in a mechanism that was dependent on dendritic cells and regulatory T cells. Encouragingly, AIP-2 also reduced activation of human dendritic cells and T cells, indicating that these findings may readily translate to the clinic.


In the developed world, declining prevalence of some parasitic infections correlates with increased incidence of allergic and autoimmune disorders. Moreover, experimental human infection with some parasitic worms confers protection against inflammatory diseases in phase 2 clinical trials. Parasitic worms manipulate the immune system by secreting immunoregulatory molecules that offer promise as a novel therapeutic modality for inflammatory diseases. We identify a protein secreted by hookworms, anti-inflammatory protein-2 (AIP-2), that suppressed airway inflammation in a mouse model of asthma, reduced expression of costimulatory markers on human dendritic cells (DCs), and suppressed proliferation ex vivo of T cells from human subjects with house dust mite allergy. In mice, AIP-2 was primarily captured by mesenteric CD103+ DCs and suppression of airway inflammation was dependent on both DCs and Foxp3+ regulatory T cells (Tregs) that originated in the mesenteric lymph nodes (MLNs) and accumulated in distant mucosal sites. Transplantation of MLNs from AIP-2–treated mice into naïve hosts revealed a lymphoid tissue conditioning that promoted Treg induction and long-term maintenance. Our findings indicate that recombinant AIP-2 could serve as a novel curative therapeutic for allergic asthma and potentially other inflammatory diseases.

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