Well, parasites used to be us. And now that they aren't - we are left sneezing for their return.
Our bodies attack parasites and allergens the same way. Scientists want to harness the relationship.
In 10 seconds? The prevalence of allergies is directly related to affluency and industrialization. Scientists believe that the lack of childhood diseases is causing a dramatic hyperactivity of the branch of the immune system that is normally used to fight parasites and other microbes.
It all started with good hygiene… The Hygiene Hypothesis argues that with increased hygiene – daily showers, running water, and toilets – humans encounter fewer microbes than ever, especially in childhood. In support of this idea, epidemiologists have shown that people in rural areas and less developed countries have a much lower incidence of allergies.
How does good hygiene cause allergies? Cells of the immune system that cause allergic reactions are the same as those that attack parasites. According to the hygiene hypothesis, when those cells do not have parasites to attack and are not busy fighting off the microbes that humans used to encounter as children, they can start behaving erratically.
There are additional factors that can influence an allergic response. The incidence of allergies (or not) depends on the timing of parasitic infections (childhood or adulthood), the species of parasite, whether the infection is short-term or long-term, and if the parasite causes the person to become sick.
Wait, I thought parasites always made people sick! Aren’t they bad? Parasites survive off of the nutrition of their host and are thus bad for people on the surface. In children, parasites can be especially painful and cause gastrointestinal discomfort. As people age, however, the immune system can keep the number of worms down and tolerate those remaining, and the worms and person are able to co-exist with minimal symptoms.
What are scientists doing with this information? The general idea is that if scientists can isolate certain parasitic molecules and inject them into people, then hopefully the immune system will be too busy dealing with these particles that they won't cause allergies.
So if I have bad allergies, should I give myself some worms? Probably not yet – there is too much unknown about what wormy concoction will best treat a person’s allergies. However, there is a real possibility that doctors will someday start prescribing parasitic extracts on a specific schedule to get rid of the sneezing and sniffling, and it could very well become a natural and effective solution.
Abstract: Inflammation and the genes, molecules, and biological pathways that lead to inflammatory processes influence many important and disparate biological processes and disease states that are quite often not generally considered classical inflammatory or autoimmune disorders. These include development, reproduction, aging, tumor development and tumor rejection, cardiovascular pathologies, metabolic disorders, as well as neurological and psychiatric disorders. This paper compares parallel aspects of autism and inflammatory disorders with an emphasis on asthma. These comparisons include epidemiological, morphometric, molecular, and genetic aspects of both disease types, contributing to a hypothesis of autism in the context of the immune based hygiene hypothesis. This hypothesis is meant to address the apparent rise in the prevalence of autism in the population.
Pub.: 07 Apr '07, Pinned: 18 Jun '17
Abstract: The hygiene hypothesis relies on the assumption that humans have adapted to a pathogen-rich environment that no longer exists in industrialized societies. Recent advances in molecular immunology and population genetics allow deeper insight into the evolution and co-evolution of host-pathogen interactions and, therefore, into the foundations of the hygiene hypothesis.
Pub.: 25 Feb '10, Pinned: 18 Jun '17
Abstract: The incidence of childhood Type I (insulin-dependent) diabetes mellitus has risen in parallel with that of childhood asthma, and the hygiene hypothesis proposes that this is due to reduced stimulation of the immune system by early intercurrent infection. If so, this protective effect is probably mediated by regulatory T lymphocytes. Co-evolutionary partners might have contributed to the development of this form of response, and parasites and the indigenous biota of the gut are plausible candidates. Helminths inhibit the development of atopic disease via induction of regulatory T cells and secretion of Il-10, and pinworms inhibit diabetes development in the non-obese diabetic (NOD) mouse. The most successful human helminth of the western world is the pinworm Enterobius vermicularis, and some 50% of young children in Europe and North America may have been infested around the middle of the twentieth century. Pinworms are benign, usually asymptomatic, and may have immunomodulatory properties that protect against the development of immune-mediated disorders including diabetes and asthma. Their decline in response to improved living conditions might explain a number of features of the epidemiology of childhood atopy and diabetes. The proposed role would be one of immunomodulation rather than disease induction, possibly mediated by interaction with other influences upon the development of the mucosal immune system. This hypothesis could be tested in case-control studies by the development of serological markers or skin testing. If confirmed, identification of the underlying mechanisms could open the way to new forms of immune intervention.
Pub.: 29 May '02, Pinned: 18 Jun '17
Abstract: Throughout the twentieth century, there were striking increases in the incidences of many chronic inflammatory disorders in the rich developed countries. These included autoimmune disorders such as Type 1 diabetes and multiple sclerosis. Although genetics and specific triggering mechanisms such as molecular mimicry and viruses are likely to be involved, the increases have been so rapid that any explanation that omits environmental change is incomplete. This chapter suggests that a series of environmental factors, most of them microbial, have led to a decrease in the efficiency of our immunoregulatory mechanisms because we are in a state of evolved dependence on organisms with which we co-evolved (and that had to be tolerated) as inducers of immunoregulatory circuits. These organisms ("Old Friends") are depleted from the modern urban environment. Rather than considering fetal programming by maternal microbial exposures, neonatal programming, the hygiene hypothesis, gut microbiota, and diet as separate and competing hypotheses, I attempt here to integrate these ideas under a single umbrella concept that can provide the missing immunoregulatory environmental factor that is needed to explain the recent increases in autoimmune disease.
Pub.: 18 Nov '11, Pinned: 18 Jun '17
Abstract: There is increasing evidence that helminth infections can protect the host against Th2-mediated allergic pathologies, even though helminths themselves are strong Th2 inducers. In murine model systems, alleviation of allergy is not achieved through immune deviation to Th1, but is linked to expansion of regulatory T cell activity. Parasite infection does not prevent allergen sensitisation, but restricts the Th2 effector phase responsible for inflammation. Suppression of allergic inflammation can be transferred by Treg phenotype cells from an infected, allergen-naïve animal to an uninfected, sensitized recipient. Patent allergy in humans is also known to be modulated by helminth infections, suggesting that a similar regulatory network may be controlling immunopathologic disease in man.
Pub.: 06 Oct '05, Pinned: 18 Jun '17
Abstract: The development of type 1 diabetes is influenced by both genetic and environmental factors. The current rise in the incidence of diabetes is occurring more rapidly than can be accounted for by genetic change, highlighting the influence of environmental modifiers. Considerable effort has been expended to identify infectious agents that might be responsible for this rise in incidence, but no single infectious agent has been linked to this dramatic increase in type 1 diabetes. There has been increasing interest in the possibility that infections of historical importance that might have shaped our immune systems over evolutionary time may also have played a role in down-modulating some autoimmune and allergic disorders. In this review, some of the ways in which certain organisms might have influenced the onset of autoimmunity are discussed.
Pub.: 06 Jan '09, Pinned: 18 Jun '17
Abstract: Dendritic cells (DCs) play a central role in activating CD4 T (T helper, Th) cells. As a component of their response to pathogen-associated stimuli, DCs produce cytokines and express surface molecules that provide important cues to modulate the effector functions of responding Th cells. Much is known of how DCs respond to, and influence immune response outcome to, bacterial and viral pathogens. However, relatively little is understood about how DCs respond to helminth parasites. This is an area of considerable interest since it impacts our understanding of the initiation of Th2 responses, which are stereotypically associated with helminth infections, and the regulation of allergic and autoimmune pathologies which evidence suggests are less severe or absent in individuals infected with helminths. This review attempts to summarize our understanding of the effects of helminth products on dendritic cell biology.
Pub.: 06 Jan '09, Pinned: 18 Jun '17
Abstract: Although the molecules and cells involved in triggering immune responses against parasitic worms (helminths) remain enigmatic, research has continued to implicate expansions of T-helper type 2 (Th2) cells and regulatory T-helper (T(reg)) cells as a characteristic response to these organisms. An intimate association has also emerged between Th2 responses and wound-healing functions. As helminth infections in humans are associated with a strong Th2/T(reg) immunoregulatory footprint (often termed a 'modified Th2' response), plausible links have been made to increased susceptibility to microbial pathogens in helminth-infected populations in the tropics and to the breakdowns in immunological control (allergy and autoimmunity) that are increasing in frequency in helminth-free developed countries. Removal of helminths and their anti-inflammatory influence may also have hazards for populations exposed to infectious agents, such as malaria and influenza, whose worst effects are mediated by excessive inflammatory reactions. The patterns seen in the control of helminth immunity are discussed from an evolutionary perspective. Whilst an inability to correctly regulate the immune system in the absence of helminth infection might seem highly counter-adaptive, the very ancient and pervasive relationship between vertebrates and helminths supports a view that immunological control networks have been selected to function within the context of a modified Th2 environment. The absence of immunoregulatory stimuli from helminths may therefore uncover maladaptations that were not previously exposed to selection.
Pub.: 06 Jan '09, Pinned: 18 Jun '17
Abstract: The incidence of allergic conditions continues to increase world wide. The underlying mechanisms and in particular the causes are however poorly understood. This article presents the evidence for the hygiene hypothesis which has been proposed in the debate on the causation of allergic disease.
Pub.: 17 May '06, Pinned: 18 Jun '17
Abstract: Allergic diseases have reached epidemic proportions in Western populations in the last several decades. The hygiene hypothesis proposed more than twenty years ago has helped us to understand the epidemic and has been verified with numerous studies. However, translational measures deduced from these studies to prevent allergic diseases have not proven effective. Recent studies on immigrants' allergies and any potential association between oral infection and allergic diseases prompt me to propose a specific hygiene hypothesis to explain how oral hygiene practices might have contributed to the uprising of hay fever, the most common allergic disease. The historic oral hygiene level in US is closely associated with the emerging allergic epidemic. Future studies to test the hypothesis are needed and verification of the hypothesis can potentially yield highly effective measures to prevent allergic diseases.
Pub.: 04 Jul '16, Pinned: 18 Jun '17
Abstract: The original hygiene hypothesis proposed that reductions in family size and exposure to childhood infections were responsible for the rise in atopic diseases. Numerous epidemiologic and longitudinal studies have been performed to test this hypothesis, which has evolved in response to these findings and emerging concepts related to the innate immune response and immunoregulatory mechanisms. Collectively, these advances raise hope that the concepts espoused in original hygiene hypothesis may soon lead to new preventive approaches to atopic diseases.
Pub.: 10 May '05, Pinned: 18 Jun '17
Abstract: The hygiene hypothesis proposes that the stimulation of the immune system by microbes or microbial products protects from the development of inflammatory diseases; therefore a reduced exposure to infectious agents may explain the rise in allergic and autoimmune diseases in industrialized countries. The contribution of studies on parasites and allergy to our understanding of the hygiene hypothesis has been two-fold. First, several studies have shown an inverse association between exposure to (Toxplasma gondii) or harbouring of parasites (Schistosoma or Intestinal helminths) and allergy. Second, the mechanisms behind such protective effects have provided new insights and theories on the ability of parasite derived molecules to down-regulate immune responses and thereby to control inflammatory diseases such as allergies. In this review, recent findings and new concepts relating to the associations between parasites and allergies at the epidemiological, cellular and molecular level are discussed.
Pub.: 03 Feb '04, Pinned: 18 Jun '17
Abstract: Man has moved rapidly from the hunter-gatherer environment to the living conditions of the rich industrialized countries. The hygiene hypothesis suggests that the resulting changed and reduced pattern of exposure to microorganisms has led to disordered regulation of the immune system, and hence to increases in certain inflammatory disorders. The concept began with the allergic disorders, but there are now good reasons for extending it to autoimmunity, inflammatory bowel disease, neuroinflammatory disorders, atherosclerosis, depression associated with raised inflammatory cytokines, and some cancers. This review discusses these possibilities in the context of Darwinian medicine, which uses knowledge of evolution to cast light on human diseases. The Darwinian approach enables one to correctly identify some of the organisms that are important for the 'Hygiene' or 'Old Friends' hypothesis, and to point to the potential exploitation of these organisms or their components in novel types of prophylaxis with applications in several branches of medicine.
Pub.: 06 Jan '09, Pinned: 18 Jun '17
Abstract: The 'hygiene hypothesis' was first proposed by Strachan in 1989 suggesting that infections and unhygienic contact with older siblings or through other exposures may confer protection from the development of allergic illnesses. This hypothesis has evolved in various ways exploring the role of overt viral and bacterial infections, the significance of environmental exposure to microbial compounds, and their effect on underlying responses of innate and adaptive immunity. So far a truly unifying concept is still lacking, but various pieces of a complex interplay between a host's immune response, characteristics of the invading microorganism, the level and variety of the environmental exposure, and the interactions between a genetic background and a range of exposures become apparent. All these pieces eventually assemble to the clinical presentation of a complex syndrome namely of asthma and allergic illnesses. Even if today practical implications cannot directly be deduced from these findings, there is great potential for the development of novel preventive and therapeutic strategies in the future based on the concepts of the 'hygiene hypothesis'.
Pub.: 05 Jun '07, Pinned: 18 Jun '17
Abstract: There is much debate about the interaction between helminths and allergic disease. The "Hygiene Hypothesis," a very popular concept among scientists and the lay public, states that infections, especially during childhood, can protect against allergic diseases. Indeed, helminth infections are known to induce regulatory responses in the host that can help the control of inflammation (including allergic inflammation). However, these infections also induce type-2-associated immune responses including helminth-specific IgE that can cross-react against environmental allergens and mediate IgE-driven effector responses. Thus, it is the delicate balance between the parasites' anti- and proallergenic effects that define the helminth/allergy interface.
Pub.: 31 Aug '16, Pinned: 18 Jun '17
Abstract: In modern societies, diseases that are driven by dysregulated immune responses are increasing at an alarming pace, such as inflammatory bowel diseases and diabetes. There is an urgent need to understand these epidemiological trends, which are likely to be driven by the changing environment of the last few decades. There are complex interactions between human genetic factors and this changing environment that is leading to the increasing prevalence of metabolic and inflammatory diseases. Alterations to human gut bacterial communities (the microbiota) and lowered prevalence of helminth infections are potential environmental factors contributing to immune dysregulation. Helminths have co-evolved with the gut microbiota and their mammalian hosts. This three-way interaction is beginning to be characterized, and the knowledge gained may enable the design of new therapeutic strategies to treat metabolic and inflammatory diseases. However, these complex interactions need to be carefully investigated in the context of host genetic backgrounds to identify optimal treatment strategies. The complex nature of these interactions raises the possibility that only with highly personalized treatment, with knowledge of individual genetic and microbiota communities, will therapeutic interventions be successful for a majority of the individuals suffering from these complex diseases of immune dysregulation.
Pub.: 15 Apr '15, Pinned: 18 Jun '17
Abstract: There is increasing recognition that exposures to infectious agents evoke fundamental effects on the development and behaviour of the immune system. Moreover, where infections (especially parasitic infections) have declined, immune responses appear to be increasingly prone to hyperactivity. For example, epidemiological studies of parasite-endemic areas indicate that prenatal or early-life experience of infections can imprint an individual's immunological reactivity. However, the ability of helminths to dampen pathology in established inflammatory diseases implies that they can have therapeutic effects even if the immune system has developed in a low-infection setting. With recent investigations of how parasites are able to modulate host immune pathology at the level of individual parasite molecules and host cell populations, we are now able to dissect the nature of the host-parasite interaction at both the initiation and recall phases of the immune response. Thus the question remains - is the influence of parasites on immunity one that acts primarily in early life, and at initiation of the immune response, or in adulthood and when recall responses occur? In short, parasite immunosuppression - sooner or later?
Pub.: 23 Apr '14, Pinned: 18 Jun '17
Abstract: The increase of allergic diseases in the industrialized world has often been explained by a decline in infections during childhood. The immunological explanation has been put into the context of the functional T cell subsets known as T helper 1 (TH1) and T helper 2 (TH2) that display polarized cytokine profiles. It has been argued that bacterial and viral infections during early life direct the maturing immune system toward TH1, which counterbalance proallergic responses of TH2 cells. Thus, a reduction in the overall microbial burden will result in weak TH1 imprinting and unrestrained TH2 responses that allow an increase in allergy. This notion is contradicted by observations that the prevalence of TH1-autoimmune diseases is also increasing and that TH2-skewed parasitic worm (helminth) infections are not associated with allergy. More recently, elevations of anti-inflammatory cytokines, such as interleukin-10, that occur during long-term helminth infections have been shown to be inversely correlated with allergy. The induction of a robust anti-inflammatory regulatory network by persistent immune challenge offers a unifying explanation for the observed inverse association of many infections with allergic disorders.
Pub.: 20 Apr '02, Pinned: 18 Jun '17
Abstract: For millions of years, parasites have altered the behaviour of their hosts. Parasites can affect host behaviour by: (1) interfering with the host's normal immune-neural communication, (2) secreting substances that directly alter neuronal activity via non-genomic mechanisms and (3) inducing genomic- and/or proteomic-based changes in the brain of the host. Changes in host behaviour are often restricted to particular behaviours, with many other behaviours remaining unaffected. Neuroscientists can produce this degree of selectivity by targeting specific brain areas. Parasites, however, do not selectively attack discrete brain areas. Parasites typically induce a variety of effects in several parts of the brain. Parasitic manipulation of host behaviour evolved within the context of the manipulation of other host physiological systems (especially the immune system) that was required for a parasite's survival. This starting point, coupled with the fortuitous nature of evolutionary innovation and evolutionary pressures to minimize the costs of parasitic manipulation, likely contributed to the complex and indirect nature of the mechanisms involved in host behavioural control. Because parasites and neuroscientists use different tactics to control behaviour, studying the methods used by parasites can provide novel insights into how nervous systems generate and regulate behaviour. Studying how parasites influence host behaviour will also help us integrate genomic, proteomic and neurophysiological perspectives on behaviour.
Pub.: 12 Dec '12, Pinned: 18 Jun '17
Abstract: Anthelminthic resistance is acknowledged worldwide and is a major problem in Aotearoa New Zealand, thus alternative parasite management strategies are imperative. One Health is an initiative linking animal, human, and environmental health. Parasites, plants, and people illustrate the possibilities of providing diverse diets for stock thereby lowering parasite burdens, improving the cultural wellbeing of a local community, and protecting the environment.
Pub.: 19 Apr '16, Pinned: 18 Jun '17
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.
Pub.: 06 Jan '12, Pinned: 18 Jun '17
Abstract: There has been nearly an epidemic rise in allergic disease throughout the world. However, this significant increase in the prevalence of allergic diseases has not been reported on the African continent. There are many factors which have been offered to explain these differences, including nutrition, environmental factors and genetic contributions. In addition, these differences in allergic disease incidents have often been discussed in terms of the hygiene hypothesis. In this manuscript, we have focused our attention on specific interactions between parasitoses and allergic diseases and illustrate their interactions with socioeconomic, cultural, and sanitary realities. The data is particularly applicable to Senegal but can be extrapolated to other regions throughout the world and the results have implications for the induction of allergic disease in both western and Third World countries.
Pub.: 18 May '04, Pinned: 18 Jun '17
Abstract: Immunomodulatory components of helminths offer great promise as an entirely new class of biologics for the treatment of inflammatory diseases. Here, we discuss the emerging themes in helminth-driven immunomodulation in the context of therapeutic drug discovery. We broadly define the approaches that are currently applied by researchers to identify these helminth molecules, highlighting key areas of potential exploitation that have been mostly neglected thus far, notably small molecules. Finally, we propose that the investigation of immunomodulatory compounds will enable the translation of current and future research efforts into potential treatments for autoimmune and allergic diseases, while at the same time yielding new insights into the molecular interface of host-parasite biology.
Pub.: 10 Apr '15, Pinned: 18 Jun '17
Abstract: Worldwide, there is little overlap between the prevalence of soil-transmitted helminths and type 2 diabetes (T2D). Helminth-induced type 2 immune responses and immune regulatory network might modulate the obesity-induced activation of inflammatory pathways that are associated with the development of insulin resistance, a strong predictor of the development of T2D. However, other factors such as helminth-associated changes in adiposity and gut microbiome might also contribute to improved metabolic outcomes. In this review we summarize epidemiological evidence for the link between helminths and T2D and discuss the potential mechanisms, based on findings from experimental studies as well as the limited number of studies in humans. This article is protected by copyright. All rights reserved.
Pub.: 08 Dec '16, Pinned: 18 Jun '17
Abstract: Changing exposure to intestinal helminths, or alterations in our intestinal microbiome, have been independently proposed to underlie the increasing incidence of chronic inflammatory diseases including allergy, autoimmunity and inflammatory bowel disease (IBD) observed in developed nations. A recent study in Science links these findings by showing that intestinal helminth infection can prevent the outgrowth of a common intestinal bacterium that causes IBD in genetically susceptible mice.
Pub.: 15 Jun '16, Pinned: 18 Jun '17
Abstract: Helminths are parasitic animals that have evolved over 100,000,000 years to live in the intestinal track or other locations of their hosts. Colonization of humans with these organisms was nearly universal until the early 20th century. More than 1,000,000,000 people in less developed countries carry helminths even today. Helminths must quell their host's immune system to successfully colonize. It is likely that helminths sense hostile changes in the local host environment and take action to control such responses. Inflammatory bowel disease (IBD) probably results from an inappropriately vigorous immune response to contents of the intestinal lumen. Environmental factors strongly affect the risk for IBD. People living in less developed countries are protected from IBD. The "IBD hygiene hypothesis" states that raising children in extremely hygienic environments negatively affects immune development, which predisposes them to immunological diseases like IBD later in life. Modern day absence of exposure to intestinal helminths appears to be an important environmental factor contributing to development of these illnesses. Helminths interact with both host innate and adoptive immunity to stimulate immune regulatory circuitry and to dampen effector pathways that drive aberrant inflammation. The first prototype worm therapies directed against immunological diseases are now under study in the United States and various countries around the world. Additional studies are in the advanced planning stage.
Pub.: 06 Aug '08, Pinned: 18 Jun '17
Abstract: Parasitic worms contain potent allergens, but epidemiological and experimental studies suggest that infections with certain helminths are negatively associated with the prevalence of allergic diseases. This seeming contradiction can be addressed by using filarial tropomyosin as an example. This protein shares structural features and crossreacting B-cell epitopes with other highly allergenic invertebrate tropomyosins. Nevertheless, it usually does not provoke allergic disease in infected individuals. In addition, it is one of the most prominent candidates for an anti-nematode vaccine. Recent data suggest mechanisms that might prevent hosts from developing allergic reactions against allergens of their parasites, such as filarial tropomyosin.
Pub.: 03 May '08, Pinned: 18 Jun '17
Abstract: The prevalence of allergic and autoimmune diseases is increasing in developed countries, possibly due to reduced exposure to microorganisms in childhood (hygiene hypothesis). Epidemiological and experimental evidence in support of this hypothesis is accumulating. In this context, parasitic helminths are now important candidates for antiallergic/anti-inflammatory agents. Here we summarize antiallergic/anti-inflammatory effects of helminths together along with our own study of the effects of Schistosoma mansoni on Th17-dependent experimental arthritis. We also discuss possible mechanisms of helminth-induced suppression according to the recent advances of immunology.
Pub.: 20 Feb '10, Pinned: 18 Jun '17
Abstract: Basophils are a major source of IL-4 and IL-13, two key cytokines that orchestrate expulsion of gastrointestinal nematodes in different mouse models. Based on recent reports, this review discusses potential roles of basophils and other cells during early and late phases of the immune response against parasitic worms.
Pub.: 11 Jun '11, Pinned: 18 Jun '17
Abstract: Immune-mediated diseases (e.g. inflammatory bowel disease, asthma, multiple sclerosis and autoimmune diabetes) are increasing in prevalence and emerge as populations adopt meticulously hygienic lifestyles. This change in lifestyles precludes exposure to helminths (parasitic worms). Loss of natural helminth exposure removes a previously universal Th2 and regulatory immune biasing imparted by these organisms. Helminths protect animals from developing immune-mediated diseases (colitis, reactive airway disease, encephalitis and diabetes). Clinical trials show that exposure to helminths can reduce disease activity in patients with ulcerative colitis or Crohn's disease. This paper summarises work by multiple groups demonstrating that colonization with helminths alters immune reactivity and protects against disease from dysregulated inflammation.
Pub.: 23 Feb '07, Pinned: 18 Jun '17