Commensal Flora, is it an Unwelcomed Companion as a Triggering Factor of Autoimmune Pancreatitis?

Abstract

The etiopathogenesis of many autoimmune disorders has not been identified. The aim of this paper is to focus on the involvement of bacterial exposure, as an environmental factor, in the pathogenesis of autoimmune pancreatitis (AIP), which is broadly categorized as autoimmune disorders involving pancreatic lesions. Avirulent and/or commensal bacteria, which may have an important role(s) as initiating/progressing factors in the pathogenesis of autoimmune disorder AIP, will be emphasized.

Keywords: autoimmune disease; autoimmune pancreatitis; bacteria; commensal flora; innate immunity.

Figure 1

Hypothetical pathogenesis of AIP. Under normal condition, commensal bacteria are not pathogenic and may exist in the host from early life. However, additional factor(s) such as genetic factors would be synchronized with the existence of microorganisms, and the progression switch to generate the status of AIP would be turned on. During the initiation phase, PAMPs and/or non-pathogenic MAMPs trigger and upregulate the innate immune system. These respective PAMPs/MAMPs and DAMPs induce inflammatory response PRRs. Second, the progressive phase features the persistence of this PAMPs/MAMPs attack or stimulation by a molecular-mimicking antigen, perhaps released as DAMPs and/or exposure to or stimulation from commensal flora possessing the same antigenic epitope that the initial pathogen possessed, thereby upregulating the host immune response to the target antigen. These slowly progressive steps eventually lead to the development of autoimmune diseases. Modified from previous reports (Haruta et al., ; Yanagisawa et al., 2011).