Infectious agents have been implicated as causative or contributing factors in initiation of autoimmune diseases. We explore the alternative, that infections can render the individual more resistant to autoimmune disease. Infectious disease in the human population has undergone dramatic and rapid change in the past century. Improved sanitation and development of antibiotics and vaccines have decreased the number of infections and their length and severity, especially in developed nations.;Since the immune system has evolved in concert with the full spectrum of infectious organisms, we and others speculate that sudden change in the childhood environment (less infections) may lead to dysregulation of the immune system and increased susceptibility to both allergy and autoimmunity, a concept known as the "hygiene hypothesis".;In this work, we test the effects of several types of pathogenic exposure on the susceptibility of mice to experimental autoimmune encephalomyelitis (EAE), a mouse model for the central nervous system autoimmune disease multiple sclerosis. Schistosoma mansoni ova treatment, live Schistosoma mansoni infection and Mycobacterium bovis bacille Callmette-Guerin (BCG) infection all conferred some degree of protection from EAE. We examine the mechanisms of protection induced in each case.;In both the schistosome ova pretreatment and live schistosome infection models, we demonstrate immune deviation, induction of a Th2 cytokine environment with enhanced levels of interleukins 4, 5, and 10 and concurrent suppression of the Th1 cytokine interferon (IFN)gamma. This deviation modulates the maturation of autoimmune T-cells and suppresses their capacity to induce autoimmunity.;In mice infected with BCG, we demonstrate redirected trafficking of the T-cells responsible for initiation of autoimmune disease away from the CNS and into peripheral inflammatory sites. The redirected trafficking did not extend to all activated T-cells as we demonstrate increased numbers of activated CD4+ T-cells in the CNS of BCG infected animals. CNS antigen specific T-cells retained their capacity to produce IFNgamma, demonstrated by intracellular cytokine staining and Elispot assay.;We demonstrate evidence for the "hygiene hypothesis" in all three models that we examined. More knowledge about the interactions between infections and autoimmune disease will lead to new treatments and possibly preventive interventions in CNS autoimmunity.
展开▼
