Infection–immunity liaison: Pathogen-driven autoimmune-mimicry (PDAIM)

Autoimmunity causes pathological conditions resulting in autoimmune diseases (ADs). Although autoimmunity is a mystery, immunological dogma suggests that autoreactive cell reactivation (ACR) breaks self-tolerance and induces autoimmunity. Thus, ACR is a royal pathway for ADs. Cumulative evidence implicates environmental factors as secondary triggers of ADs in the genetically susceptible hosts. Infection is the most likely trigger. Although several mechanisms have been proposed to explain how infectious agents trigger ADs, ACR is assumed to be an essential pathway.Here, by showing some exemplary ADs, we propose two novel pathways, “molecular modification pathway” and “hyper-immune-inflammatory response pathway”, which induce AD-like conditions directly by infectious agents without ACR. These AD-like conditions are actually not true “ADs” according to the current definition. Therefore, we define them as “pathogen-driven autoimmune-mimicry (PDAIM)”. Confirming PDAIM will open perspectives in developing novel fundamental and non-immunosuppressive therapies for ADs. The idea should also provide novel insights into both the mechanisms of autoimmunity and the pathogenesis of ADs.