Helminth-modified pulmonary immune response protects mice from allergen-induced airway hyperresponsiveness

School of Biochemistry and Immunology, Trinity College, Dublin, Ireland.
The Journal of Immunology (Impact Factor: 5.36). 02/2006; 176(1):138-47. DOI: 10.4049/jimmunol.176.1.138
Source: PubMed

ABSTRACT It has been shown that the presence of certain helminth infections in humans, including schistosomes, may reduce the propensity to develop allergies in infected populations. Using a mouse model of schistosome worm vs worm + egg infection, our objective was to dissect the mechanisms underlying the inverse relationship between helminth infections and allergies. We have demonstrated that conventional Schistosoma mansoni egg-laying male and female worm infection of mice exacerbates airway hyperresponsiveness. In contrast, mice infected with only schistosome male worms, precluding egg production, were protected from OVA-induced airway hyperresponsiveness. Worm-infected mice developed a novel modified type 2 cytokine response in the lungs, with elevated allergen-specific IL-4 and IL-13 but reduced IL-5, and increased IL-10. Although schistosome worm-only infection is a laboratory model, these data illustrate the complexity of schistosome modulation of host immunity by the worm vs egg stages of this helminth, with the potential of infections to aggravate or suppress allergic pulmonary inflammation. Thus, infection of mice with a human parasitic worm can result in reduced airway inflammation in response to a model allergen.

Download full-text


Available from: Padraic Fallon, Jul 28, 2015
  • Source
    • "Infection prior to collagen challenge led to upregulation in IL-10 and decrease in IFN-c, TNF-a, IL-1b and IL-6 McInnes et al. (2003) Song et al. (2011) Allergy/Asthma H. polygyrus Inflammatory lung infiltrates from ovalbumin and Der p 1 challenge were suppressed in infected mice Wilson et al. (2005) S. mansoni Protection from Pen V-induced active systemic anaphylaxis via IL-10 producing B cells Mangan et al. (2004) Protection from allergic airway reactivity Decreased allergen-stimulated IL-5. Increased IL-10 and TGF-b production Mangan et al. (2006) Protection from Airway hyper-responsiveness via CD19 "
    [Show abstract] [Hide abstract]
    ABSTRACT: The use of live helminth infections is currently in clinical trials as a novel approach for the treatment of a range of allergic and autoimmune diseases. This rapid progression from observational studies some 20 years ago to helminth clinical trials can be attributed to huge advances in not just pre-clinical and clinical evidence, pertaining to the efficacy of these parasites in unrelated diseases, but also a greater understanding of the complex immunological mechanisms that underpin these effects. Helminths have exerted significant evolutionary selective pressures on the host immune genome or "immunome". Studies on helminths were pivotal in a paradigm shift in immunology with recent discoveries of a number of novel immune cell populations. Critically, these new discoveries highlight the need to further understand the underlying mechanism behind the desirable therapeutic effects that helminths offer. With these unknown unknowns there is the distinct possibility that a true, fundamental modus operandi for helminth therapy will arrive long after it has been established in the clinic.
    International journal for parasitology 01/2013; 43(3-4). DOI:10.1016/j.ijpara.2012.12.002 · 3.40 Impact Factor
  • Source
    • "Reduced IL-5, increased IL-10 and evidence for B cell involvement Mangan et al. (2006) S. mansoni (eggs, ip.) "
    [Show abstract] [Hide abstract]
    ABSTRACT: Helminth parasites are masters of immune regulation; a likely prerequisite for long-term survival by circumventing their hosts' attempt to eradicate them. From a translational perspective, knowledge of immune events as a response to infection with a helminth parasite could be used to reduce the intensity of unwanted inflammatory reactions. Substantial data have accumulated showing that inflammatory reactions that promote a variety of auto-inflammatory diseases are dampened as a consequence of infection with helminth parasites, via either the mobilization of an anti-worm spectrum of immune events or by the direct effect of secretory/excretory bioactive immunomodulatory molecules released from the parasite. However, many issues are outstanding in the definition of the mechanism(s) by which infection with helminth parasites can affect the outcome, positively or negatively, of concomitant disease. We focus on a subgroup of this complex group of metazoan parasites, the cestodes, summarizing studies from rodent models that illustrate if, and by what mechanisms, infection with tapeworms ameliorate or exaggerate disease in their host. The ability of infection with cestodes, or other classes of helminth, to worsen a disease course or confer susceptibility to intracellular pathogens should be carefully considered in the context of 'helminth therapy'. In addition, poorly characterised cestode extracts can regulate murine and human immunocyte function, yet the impact of these in the context of autoimmune or allergic diseases is poorly understood. Thus, studies with cestodes, as representative helminths, have helped cement the concept that infection with parasitic helminths can inhibit concomitant disease; however, issues relating to long-term effects, potential side-effects, mixed pathogen infections and purification of immunomodulatory molecules from the parasite remain as challenges that need to be addressed in order to achieve the use of helminths as anti-inflammatory agents for human diseases.
    International journal for parasitology 10/2012; 43(3-4). DOI:10.1016/j.ijpara.2012.09.005 · 3.40 Impact Factor
  • Source
    • "Oxazolone-(Oxa-) induced skin immediate hypersensitivity OVA-induced AHR Mast cell mediated, TLR4-dependent [72] Helminth infection and undefined products S. mansoni infection; males and females + eggs laid in infection; males (no eggs) Pen V-induced systemic anaphylaxis IL-10-producing B cells [73] S. mansoni infection; males (no eggs) OVA-induced AHR B cell-and IL-10-dependent suppression of pulmonary eosinophil infiltration [74] S. mansoni infection; eggs OVA-induced AI Egg-treatment: CD4 + CD25 + Foxp3 + Treg [75] S. japonicum egg antigen (SEA) OVA-induced AI CD4 + CD25 + Treg, possibly IL-10 [76] A. suum adult worm extract (ASC) OVA-induced AHR NA [77] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Helminths are master regulators of host immune responses utilising complex mechanisms to dampen host protective Th2-type responses and favour long-term persistence. Such evasion mechanisms ensure mutual survival of both the parasite and the host. In this paper, we present recent findings on the cells that are targeted by helminths and the molecules and mechanisms that are induced during infection. We discuss the impact of these factors on the host response as well as their effect in preventing the development of aberrant allergic inflammation. We also examine recent findings on helminth-derived molecules that can be used as tools to pinpoint the underlying mechanisms of immune regulation or to determine new anti-inflammatory therapeutics.
    BioMed Research International 12/2011; 2011:821578. DOI:10.1155/2011/821578 · 2.71 Impact Factor
Show more