title: SJL mice infected with Acanthamoeba castellanii develop central nervous system autoimmunity through the generation of cross-reactive T cells for myelin antigens.
abstract: We recently reported that Acanthamoeba castellanii (ACA), an opportunistic pathogen of the central nervous system (CNS) possesses mimicry epitopes for proteolipid protein (PLP) 139-151 and myelin basic protein 89-101, and that the epitopes induce experimental autoimmune encephalomyelitis (EAE) in SJL mice reminiscent of the diseases induced with their corresponding cognate peptides. We now demonstrate that mice infected with ACA also show the generation of cross-reactive T cells, predominantly for PLP 139-151, as evaluated by T cell proliferation and IAs/dextramer staining. We verified that PLP 139-151-sensitized lymphocytes generated in infected mice contained a high proportion of T helper 1 cytokine-producing cells, and they can transfer disease to naïve animals. Likewise, the animals first primed with suboptimal dose of PLP 139-151 and later infected with ACA, developed EAE, suggesting that ACA infection can trigger CNS autoimmunity in the presence of preexisting repertoire of autoreactive T cells. Taken together, the data provide novel insights into the pathogenesis of Acanthamoeba infections, and the potential role of infectious agents with mimicry epitopes to self-antigens in the pathogenesis of CNS diseases such as multiple sclerosis.
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: Chandirasegaran
authors.initials: C
authors.lastname: Massilamany
authors.affiliation: Virginia Commonwealth University School of Medicine, Richmond, Virginia, United States of America.
authors.forename: Francine
authors.initials: F
authors.lastname: Marciano-Cabral
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Bruno da
authors.initials: Bd
authors.lastname: Rocha-Azevedo
authors.affiliation: Virginia Commonwealth University School of Medicine, Richmond, Virginia, United States of America.
authors.forename: Melissa
authors.initials: M
authors.lastname: Jamerson
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: Arunakumar
authors.initials: A
authors.lastname: Gangaplara
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Steffen
authors.affiliation: University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Rana
authors.initials: R
authors.lastname: Zabad
authors.affiliation: University of Pecs, Pecs, Hungary; University of Southern Denmark, Odense, Denmark.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Illes
authors.affiliation: Stanford University School of Medicine, Stanford, California and VA Health Care System, Palo Alto, California, United States of America.
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Sobel
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: Jay
authors.initials: J
authors.lastname: Reddy
mesh_terms: D048248:Acanthamoeba castellanii / Q000276:immunology*; D000562:Amebiasis / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009103:Multiple Sclerosis / Q000276:immunology; D018991:Myelin Proteolipid Protein / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000941:Antigens; D000939:Epitopes; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151)