Mini-reviewHelminths and our immune system: Friend or foe?
Introduction
Helminth infections are amongst the most common infections of humans and are notoriously chronic in nature, with some species of worms surviving within their host for many years, in some cases even decades. In order to facilitate such longterm survival within an immunocompetent host these organisms have developed sophisticated survival strategies, including the ability to modulate and manipulate our immune system. This ability to alter immune responses could be of detriment to the host if it interferes with the development of protective immune responses against other infections. However, since helminths and the human immune system have co-evolved over millennia it has also been suggested that helminth infections may have a beneficial role in controlling autoimmune and other excessive inflammatory responses and that these organisms may even provide a source of novel anti-inflammatory therapeutics. Parasitic helminth infections may therefore constitute a double-edged sword for human health and it is of vital importance to clarify any beneficial or detrimental roles these infections may have on public health, in addition to their role as single infections.
Section snippets
Helminths and the immune system
The mammalian immune system is a carefully tuned orchestra consisting of a large number of different members, producing humoral (antibody) and cellular immunity. Central to most of the immune functions are T helper (Th) cells. Th cells play a critical part in instructing and controlling the various players of the immune response against invading pathogens. Several different types of T helper cells exist, primarily based on the type of cytokines they produce. Th1 cells secrete IFN-γ, are
Helminths and allergic disorders
Allergic diseases include asthma, atopic dermatitis and rhinitis. These are inflammatory diseases caused by immune reactivity to environmental allergens. The prevalence of allergic disease is generally low in rural areas of Europe [5] and in developing countries [6], while they are considered an increasingly important cause of morbidity in westernized countries. It is clear that children with several older siblings or attending day care have a reduced risk of developing allergies [7] and a
Helminths and vaccination
Many modern vaccines are designed to induce a Th1 response for optimal efficiency. Since helminth infections in general induce either a Th2 or a regulatory response, or both, there has been much discussion and speculation on whether concurrent helminth infections are responsible for reducing vaccine efficacy. Clear evidence exist from murine models that helminth infections can alter the nature of immune responses to non-parasite or ‘third-party’ antigens [67], [68], [69] via the skewing of the
Concluding remarks
There is now little doubt that helminth infections really do have the ability to influence the development of immune responses. Both animal and human studies have demonstrated this repeatedly and convincingly. However, what remains to be established is if this ability is of any real public health significance. It is clear that many studies are still conduced based on assumptions regarding what is probably a somewhat simplistic immunological view of helminths, who tend to be generally lumped
Acknowledgements
This work was supported by a Wellcome trust grant and a RCUK fellowship. I would like to thank Dr Quentin Bickle and Prof. Eleanor Riley for helpful discussions.
References (103)
Urbanization and childhood asthma: an African perspective
J Allergy Clin Immunol
(2000)Allergies, infections and the hygiene hypothesis—the epidemiological evidence
Immunobiology
(2007)- et al.
Reduced risk of atopy among school-age children infected with geohelminth parasites in a rural area of the tropics
J Allergy Clin Immunol
(2003) - et al.
Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10
Lancet
(2000) - et al.
Effect of anthelmintic treatment on the allergic reactivity of children in a tropical slum
J Allergy Clin Immunol
(1993) - et al.
Effect of albendazole treatments on the prevalence of atopy in children living in communities endemic for geohelminth parasites: a cluster-randomised trial
Lancet
(2006) - et al.
Protective effect of Schistosoma mansoni infection on allergic airway inflammation depends on the intensity and chronicity of infection
J Allergy Clin Immunol
(2007) - et al.
Respiratory virus-induced regulation of asthma-like responses in mice depends upon CD8 T cells and interferon-gamma production
Am J Pathol
(2007) Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences
Gastroenterology
(2004)- et al.
Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease
Am J Gastroenterol
(2003)
Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial
Gastroenterology
Schistosoma japonicum eggs modulate the activity of CD4+ CD25+ Tregs and prevent development of colitis in mice
Exp Parasitol
Helminth infection enhances disease in a murine TH2 model of colitis
Gastroenterology
Trichinella spiralis: modulation of experimental autoimmune encephalomyelitis in DA rats
Exp Parasitol
Soluble egg antigen from Schistosoma japonicum modulates the progression of chronic progressive experimental autoimmune encephalomyelitis via Th2-shift response
J Neuroimmunol
Helminth infection suppresses T-cell immune response to HIV–DNA-based vaccine in mice
Vaccine
Schistosoma mansoni infection reduces the protective efficacy of BCG vaccination against virulent Mycobacterium tuberculosis
Vaccine
Increased frequency of malaria attacks in subjects co-infected by intestinal worms and Plasmodium falciparum malaria
Trans R Soc Trop Med Hyg
Severe malaria attack is associated with high prevalence of Ascaris lumbricoides infection among children in rural Senegal
Trans R Soc Trop Med Hyg
Anemia in mice with concomitant Schistosoma mansoni and Plasmodium berghei yoelii infection
Trans Roy Soc Trop Med Hyg
Concurrent gastro-intestinal nematode infection does not alter the development of experimental cerebral malaria
Microbes Infect
Transforming growth factor-beta ‘reprograms’ the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset
Nat Immunol
Severe CD4 T cell-mediated immunopathology in murine schistosomiasis is dependent on IL-12p40 and correlates with high levels of IL-17
J Immunol
Protective immune mechanisms in helminth infection
Nat Rev Immunol
Helminth parasites—masters of regulation
Immunol Rev
Environmental exposure to endotoxin and other microbial products and the decreased risk of childhood atopy: evaluating developments since April 2002
Curr Opin Allergy Clin Immunol
The germless theory of allergic disease: revisiting the hygiene hypothesis
Nat Rev Immunol
Inverse association between skin response to aeroallergens and Schistosoma mansoni infection
Int Arch Allergy Immunol
Wheezing, allergy, and parasite infection in children in urban and rural Ethiopia
Am J Respir Crit Care Med
Impaired T helper 2 response to aeroallergen in helminth-infected patients with asthma
J Infect Dis
Long-term treatment of intestinal helminths increases mite skin-test reactivity in Gabonese schoolchildren
J Infect Dis
Bronchoconstriction in helminthic infection
Int Arch Allergy Immunol
Clinical improvement of asthma after anthelminthic treatment in a tropical situation
Am J Respir Crit Care Med
Helminth infection during pregnancy and development of infantile eczema
JAMA
Efficacy of current drugs against soil-transmitted helminth infections: systematic review and meta-analysis
JAMA
No audible wheezing: nuggets and conundrums from mouse asthma models
J Exp Med
Infection of mice with the helminth Strongyloides stercoralis suppresses pulmonary allergic responses to ovalbumin
Clin Exp Allergy
Suppression of allergic airway inflammation by helminth-induced regulatory T cells
J Exp Med
Intestinal helminths protect in a murine model of asthma
J Immunol
Helminth infection modulates the development of allergen-induced airway inflammation
Int Immunol
Helminth-derived products inhibit the development of allergic responses in mice
Am J Respir Crit Care Med
Helminth infection with Litomosoides sigmodontis induces regulatory T cells and inhibits allergic sensitization, airway inflammation, and hyperreactivity in a murine asthma model
J Immunol
Inhibition of Fc epsilon RI-mediated mast cell responses by ES-62, a product of parasitic filarial nematodes
Nat Med
A helminth immunomodulator reduces allergic and inflammatory responses by induction of IL-10-producing macrophages
J Immunol
Helminth-modified pulmonary immune response protects mice from allergen-induced airway hyperresponsiveness
J Immunol
Schistosoma japonicum infection modulates the development of allergen-induced airway inflammation in mice
Parasitol Res
Schistosoma japonicum egg antigens stimulate CD4 CD25 T cells and modulate airway inflammation in a murine model of asthma
Immunology
Infection with the roundworm Toxocara canis leads to exacerbation of experimental allergic airway inflammation
Clin Exp Allergy
Differential modulation of allergic eye disease by chronic and acute Ascaris infection
Invest Ophthalmol Vis Sci
Ascaris suum-derived products suppress mucosal allergic inflammation in an interleukin-10-independent manner via interference with dendritic cell function
Infect Immun
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