Autoimmunity in the Mediation of Granulomatous Amoebic Encephalitis: Implications for Therapy

Abstract

Acanthamoeba spp. are free-living amoebae that are ubiquitous in the environment. Most healthy individuals carry Acanthamoeba-reactive antibodies, suggesting constant exposure to amoebae. In spite of the high prevalence of the amoebae, the incidence of diseases caused by Acanthamoeba is very low. Non-opportunistically, Acanthamoebae can induce keratitis in healthy humans, but as an opportunistic pathogen, the amoebae can cause fatal encephalitis especially in immunocompromised individuals and treatments are often ineffective. Amoebic encephalitis is a life-threatening disease of the central nervous system (CNS) caused by free-living amoebae belonging to the genera Acanthamoeba, Balamuthia and Naegleria. Because they lack host-specificity, the ubiquitous amoebae can infect a wide range of species (Marciano-Cabral & Cabral, 2003, Schuster & Visvesvara, 2004). The diseases caused by Acanthamoeba spp. and Balamuthia spp. are generally termed ”granulomatous amoebic encephalitis” (GAE), whereas those caused by Naegleria spp. are called ‘primary amoebic meningioencephalitis (PAM)’(Marciano-Cabral & Cabral, 2003, Schuster & Visvesvara, 2004, Khan, 2006, da Rocha-Azevedo, et al., 2009). While Acanthamoebae induce illness mostly in immunocompromised individuals, Balamuthia spp. and Naegleria spp. can cause diseases in both immune-sufficient and immune-deficient individuals (Martinez & Visvesvara, 2001, Marciano-Cabral & Cabral, 2003, Schuster & Visvesvara, 2004, Khan, 2006, da Rocha-Azevedo, et al., 2009). Nevertheless, all of them can induce keratitis in healthy individuals, often in contact lens-wearers (Jones, et al., 1975, Martinez & Visvesvara, 1997, Marciano-Cabral & Cabral, 2003, da Rocha-Azevedo, et al., 2009). We recently discovered that A. castellanii contains mimicry sequence for immunodominant epitope of CNS myelin proteolipid protein (PLP), suggesting that exposure to A. castellanii can lead to the generation of autoimmune responses by antigenic mimicry. In this review, we discuss our understanding of the pathophysiology of Acanthamoeba-induced encephalitis, with a special emphasis on autoimmunity in mediation of the disease, and implications for therapy.