title: The role of primary infection of Schwann cells in the aetiology of infective inflammatory neuropathies.
abstract: Numerous different pathogens are responsible for infective peripheral neuropathies and this is generally the result of the indirect effects of pathogen infection, namely anti pathogen antibodies cross reacting with epitopes on peripheral nerve, auto reactive T cells attacking myelin, circulating immune complexes and complement fixation. Primary infection of Schwann cells (SC) associated with peripheral nerve inflammation is rare requiring pathogens to cross the Blood Peripheral Nerve Barrier (BPNB) evade anti-pathogen innate immune pathways and invade the SC. Spirochetes Borrelia bourgdorferi and Trepomema pallidum are highly invasive, express surface lipo proteins, but despite this SC are rarely infected. However, Trypanosoma cruzi (Chaga's disease) and Mycobacterium leprae. Leprosy are two important causes of peripheral nerve infection and both demonstrate primary infection of SC. This is due to two novel strategies; T. cruzi express a trans-silalidase that mimics host neurotrophic factors and infects SC via tyrosine kinase receptors. M. leprae demonstrates multi receptor SC tropism and subsequent infection promotes nuclear reprogramming and dedifferentiation of host SC into progenitor stem like cells (pSLC) that are vulnerable to M. leprae infection. These two novel pathogen evasion strategies, involving stem cells and receptor mimicry, provide potential therapeutic targets relevant to the prevention of peripheral nerve inflammation by inhibiting primary SC infection.
authors.affiliation: Infection and Immunity, Henry Wellcome Building, Cardiff University, Cardiff CF14 4XN, United Kingdom. Electronic address: jwneal@doctors.org.uk.
authors.forename: J W
authors.initials: JW
authors.lastname: Neal
authors.affiliation: Laboratoire d'Immunologie Clinique et Expérimentale de l'OI (LICE-OI), Centre recherche Immuno-clinique des agents pathogènes de l'OI (CRIC-AP OI) Pôle Biologie Santé, Hôpital Félix Guyon, CHU de la Réunion, Reunion. Electronic address: philippe.gasque@chu-reunion.fr.
authors.forename: P
authors.initials: P
authors.lastname: Gasque
mesh_terms: D014355:Chagas Disease; D006801:Humans; D007249:Inflammation / Q000382:microbiology; D007918:Leprosy; D008264:Macrophages; D009166:Mycobacterium leprae / Q000472:pathogenicity; D010523:Peripheral Nervous System Diseases / Q000382:microbiology*; D012583:Schwann Cells / Q000382:microbiology* / Q000502:physiology*; D013234:Stem Cells / Q000382:microbiology / Q000502:physiology; D014349:Trypanosoma cruzi / Q000472:pathogenicity
keywords: Pathogens; Peripheral neuropathy; Schwann cell; Stem cell