The Schistosoma mansoni T2 ribonuclease omega-1 modulates inflammasome-dependent IL-1ß secretion in macrophages.

The T2 ribonuclease omega-1 is a powerful Th2-inducing factor secreted by the eggs of the blood fluke Schistosoma mansoni. Omega-1 can modulate pattern recognition receptor-induced inflammatory signatures and alter antigen presentation by dendritic cells. Recent findings have suggested that component(s) contained in or secreted by S. mansoni eggs (soluble egg antigen) can also enhance IL-1ß secretion by dendritic cells stimulated with pattern recognition receptor ligands. Here we show that omega-1 enhances IL-1ß secretion in macrophages stimulated with Toll-like receptor 2 ligand, and propose omega-1 as the factor in soluble egg antigen capable of regulating inflammasome activity. This effect is dependent on the C-type lectin receptor Dectin-1, caspase-8 and the ASC inflammasome adaptor protein, highlighting the ability of omega-1 to regulate multiple pattern recognition receptor signalling pathways. These mechanistic insights into manipulation of host immunity by a parasite product have implications for the design of anti-inflammatory therapeutic drugs.

Helminth infection and type 1 diabetes.

The increasing incidence of type 1 diabetes (T1D) and autoimmune diseases in industrialized countries cannot be exclusively explained by genetic factors. Human epidemiological studies and animal experimental data provide accumulating evidence for the role of environmental factors, such as infections, in the regulation of allergy and autoimmune diseases. The hygiene hypothesis has formally provided a rationale for these observations, suggesting that our co-evolution with pathogens has contributed to the shaping of the present-day human immune system. Therefore, improved sanitation, together with infection control, has removed immunoregulatory mechanisms on which our immune system may depend. Helminths are multicellular organisms that have developed a wide range of strategies to manipulate the host immune system to survive and complete their reproductive cycles successfully. Immunity to helminths involves profound changes in both the innate and adaptive immune compartments, which can have a protective effect in inflammation and autoimmunity. Recently, helminth-derived antigens and molecules have been tested in vitro and in vivo to explore possible applications in the treatment of inflammatory and autoimmune diseases, including T1D. This exciting approach presents numerous challenges that will need to be addressed before it can reach safe clinical application. This review outlines basic insight into the ability of helminths to modulate the onset and progression of T1D, and frames some of the challenges that helminth-derived therapies may face in the context of clinical translation.

Autoimmunity and inflammation: murine models and translational studies.

Autoimmune and inflammatory diseases, including type 1 diabetes, multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis, constitute an important and growing public health burden. However, in many cases our understanding of disease biology is limited and available therapies vary greatly in their efficacy and safety. Animal models of autoimmune and inflammatory diseases have provided valuable tools to researchers investigating their aetiology, pathology, and novel therapeutic strategies. Although such models vary in the degree to which they reflect human autoimmune and inflammatory diseases and caution is required in the extrapolation of animal data to the clinical setting, therapeutic approaches first evaluated in established animal models, including collagen-induced arthritis, experimental autoimmune encephalomyelitis, and the nonobese diabetic mouse, have successfully progressed to clinical investigation and practice. Similarly, these models have proven useful in providing support for basic hypotheses regarding the underlying causes and pathology of autoimmune and inflammatory diseases. Here we review selected murine models of autoimmunity and inflammation and efforts to translate findings from these models into both basic insights into disease biology and novel therapeutic strategies.

Idiopathic environmental intolerances.

Health concerns related to the quality of the environment in offices, schools, homes, and residences have increased dramatically over the past 2 decades. One health problem frequently confronting medical practitioners and often attributed to environmental quality problems is idiopathic environmental intolerances (IEI). Formerly known as multiple chemical sensitivities, IEI is an acquired disorder characterized by adverse reactions attributed to exposure to a variety of substances under ordinary conditions. Alleged precipitants include solvents, pesticides, detergents, dusts, and fragrances. Symptoms include fatigue, malaise, headache, concentration and memory difficulties, lightheadedness, cough, hoarseness, and rhinitis without objective physical signs or consistent laboratory abnormalities. The role of the environment in precipitating these complaints continues to be controversial, and no intervention or treatment has thus far been proven to be effective. While not progressive or life threatening, IEI is often functionally disabling and very distressing to affected individuals. The investigation of IEI should involve, at a minimum, a clinical evaluation of the affected person and in most cases an environmental evaluation as well. IEI should be managed without overutilization of diagnostic tests or prescription of unnecessary environmental, occupational, or dietary restrictions.