Infection and autoimmunity: Lessons of animal models

Abstract

While the key initiating processes that trigger human autoimmune diseases remain enigmatic, increasing evidences support the concept that microbial stimuli are among major environmental factors eliciting autoimmune diseases in genetically susceptible individuals.Here, we present an overview of evidences obtained through various experimental models of autoimmunity for the role of microbial stimuli in disease development. Disease onset and severity have been compared in numerous models under conventional, specific-pathogen-free and germ-free conditions. The results of these experiments suggest that there is no uniform scheme that could describe the role played by infectious agents in the experimental models of autoimmunity. While some models are dependent, others prove to be completely independent of microbial stimuli. In line with the threshold hypothesis of autoimmune diseases, highly relevant genetic factors or microbial stimuli induce autoimmunity on their own, without requiring further factors. Importantly, recent evidences show that colonization of germ-free animals with certain members of the commensal flora [such as segmented filamentous bacteria (SFB)] may lead to autoimmunity. These data drive attention to the importance of the complex composition of gut flora in maintaining immune homeostasis. The intriguing observation obtained in autoimmune animal models that parasites often confer protection against autoimmune disease development may suggest new therapeutic perspectives of infectious agents in autoimmunity.Keywords: autoimmunity, mimicry, infection, microbe, model * These authors contributed equally. **Corresponding author: Edit Buzas; Department of Genetics, Cell-and Immunobiology, Semmelweis University, H-1089 Budapest, Nagyvárad tér 4, Hungary; Phone: +36-30-7444918; E-mail: edit.buzas@gmail.com Experimental models of autoimmunityInbred mice have proven to be extremely successful tools for basic immunology research. However, data argue for substantial differences between the immune systems of rodents and humans, and because of this, mice or rats have been recently considered of somewhat limited relevance as models of disease [4,5]. However, despite all limitations, experimental models enable targeting fundamental questions such as the implication of infectious agents in autoimmune disease development.Most human autoimmune diseases are characterized by complex genetics; a combination of numerous alleles confers genetic susceptibility for a given disease along with epigenetic and environmental factors. Exceptions include the rare monogenic autoimmune diseases such as the APECED (Autoimmune polyendocrinopthy-candidiasisectodermal dystrophy) and IPEX (Immunodysregulation polyendocrinopathy enteropathy X-linked) syndromes in which the mutation of genes with outstanding impact on immune tolerance (AIRE and FoxP3) leads to pathological autoimmunity. Experimental autoimmune models are in agreement with the above interpretation of the basis of human autoimmunity. They include two basic categories: induced ...

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Effects of Klebsiella pneumoniae on Toll-Like Receptor-Dependent Endoplasmic Reticulum Stress-Related Signaling Pathways and Gene Expression and Promotes HLA-B27 Misfolding

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