Modelling gene-environment interactions in Th1- and Th2-dominated diseases of laboratory animals.
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Animals↗
Biomedical subjects
L Rosa Brunet
Publications and source records attributed to L Rosa Brunet.
Intragastric administration of Mycobacterium vaccae inhibits severe pulmonary allergic inflammation in a mouse model.
BACKGROUND: Coexistence with harmless microorganisms such as lactobacilli, saprophytic mycobacteria and some helminths, throughout evolution, may have shaped the host immune system. Exposure to such organisms may have therapeutic benefits by triggering immunoregulatory mechanisms that control inappropriate immune responses to self, gut contents or allergens. OBJECTIVE: We determined whether treatment with Mycobacterium vaccae by gavage influences the host immune response both locally and systemically. We also investigated whether delivery by this route prevents severe symptoms of disease in a murine model of pulmonary allergic inflammation. RESULTS: A single intragastric administration of M. vaccae induced a transient increase in the production of IL-10 and IFN-gamma by mesenteric lymph nodes cells and splenocytes. In addition, in a mouse model of pulmonary allergic inflammation, a single treatment with M. vaccae by gavage not only diminished the total cellular infiltrate and the eosinophilic component induced by subsequent intratracheal allergen challenge, but also biased local and systemic cytokine production towards IL-10. Delivery of M. vaccae by gavage was as effective as subcutaneous treatment. CONCLUSION: This is the first report to suggest that heat-killed mycobacteria can down-regulate symptoms of allergic inflammation by the intragastric route. These data suggest an alternative route of treatment with M. vaccae for patients with allergic conditions.
Administration, Oral↗
Mycobacteria and other environmental organisms as immunomodulators for immunoregulatory disorders.
In the rich, developed parts of the world there has been a steady and simultaneous increase in at least three groups of disease: (1) allergies, (2) inflammatory bowel diseases (IBD; e.g. Crohn's disease and ulcerative colitis) and (3) autoimmunity (e.g. type 1 diabetes and multiple sclerosis). Because the medical world is so compartmentalised it was some time before the connection between these increases was noticed and understood. There is now evidence that the simultaneous increase in these diseases of immunodysregulation is at least partly attributable to malfunction of regulatory T cells (Treg). This paper provides an overview of relevant work in each of these fields of medicine (though with emphasis on the allergic disorders), and concludes that the increasing failure of Treg is a consequence of diminished exposure to certain micro-organisms that are "old friends", because of their continuous presence throughout mammalian evolution. These organisms, which include saprophytic mycobacteria, helminths and lactobacilli, are recognised by the innate immune system as harmless, and as adjuvants for Treg induction. Polymorphisms of components of the innate immune system such as TLR2 and NOD2 appear to define subsets of the population that will develop immunoregulatory disorders when living in the modern environment. A further role of the "old friends" and of the Treg that they induce might be to maintain the levels of regulatory IL-10 secreting macrophages and antigen-presenting cells, which are depleted in asthma and Crohn's disease. These concepts are leading to novel therapies based on harmless organisms or their components. Phase I/II clinical trials have yielded some statistically significant results, and phase II trials are in progress.
Adjuvants, Immunologic↗
Paneth and intermediate cell hyperplasia induced in mice by helminth infections.
Hyperplasia of Paneth and intermediate cells is a recently described component of the response of the small intestine of mice to infection with the nematode Trichinella spiralis. To investigate whether this hyperplasia is parasite specific or represents a generic intestinal response to infection, mice were infected with T. spiralis, Nippostrongylus brasiliensis, Heligmosomoides polygyrus or Schistosoma mansoni and tissue samples taken at various time-points post-infection to determine Paneth and intermediate cell numbers. All infections induced Paneth and intermediate cell hyperplasia, but the patterns of response varied between the parasite species concerned, reflecting differences in their relationships with the host. Increases in the numbers of these cells appeared to correlate with known patterns of T-helper-2 immune responses.
Animals↗
Effects on the neutral lipid contents of the liver, ileum and serum during experimental schistosomiasis.
During infection of vertebrate hosts with Schistosoma mansoni,worm eggs trapped in host tissues induce granulomatous lesions that interfere with normal organ functions. Even though both the liver and the intestine are particularly susceptible to egg-induced tissue damage, little information is available on the pathobiochemical changes induced in these organs during infection. Using a mouse model, we investigated whether the lipid profiles of the liver and ileum were altered significantly as a result of infection. We found that triacylglycerol and cholesteryl ester levels decreased significantly as infection progressed.
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