title: Infections and Systemic Lupus Erythematosus: Binding or Sparring Partners?
abstract: Extensive work on experimental animal models clearly demonstrates that infectious agents can break immunological tolerance to self-antigens and induce autoimmune disorders, mainly systemic lupus erythematosus (SLE). The establishment of a causative link between infections and autoimmunity has been largely studied in a host of clinical studies, proving the role of infectious agents in the induction, as well as in the progression or exacerbation of SLE. However, we are far from a plain understanding of microbial-host interactions in the pathogenesis of SLE. Much serological, molecular and geoepidemiological evidence supports the relationship of different environmental infectious triggers in the inception of SLE-related autoimmune phenomena with adjuvant effects. The promotion of autoimmune responses through bystander activation or epitope spreading via multiple inflammatory pathways has been confirmed in animal models. Different viruses have been implicated in SLE pathogenesis, particularly Epstein-Barr virus, but also parvovirus B19, cytomegalovirus and retroviruses. SLE patients usually have an impaired immune response towards Epstein-Barr virus and dysregulation of the viral latency period. Furthermore, the accumulation of endogenous retroviral products might trigger the production of interferon and anti-DNA antibodies. In addition, protozoan infections might even protect from autoimmune processes and rescind an ongoing B cell activation. Herein, we discuss which type of infections induce, exacerbate or inhibit autoimmune disorders and analyze the principal infection-induced immunological mechanisms influencing the development of SLE.
authors.affiliation: Institute of Pediatrics, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, 00168 Rome, Italy. drigante@rm.unicatt.it.
authors.forename: Donato
authors.initials: D
authors.lastname: Rigante
authors.affiliation: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy. susanna.esposito@unimi.it.
authors.forename: Susanna
authors.initials: S
authors.lastname: Esposito
mesh_terms: D000818:Animals; D015551:Autoimmunity; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology* / Q000821:virology; D014777:Virus Diseases / Q000150:complications / Q000276:immunology*
keywords: Epstein-Barr virus; cytomegalovirus; parvovirus B19; retrovirus; systemic lupus erythematosus