SJL mice infected with Acanthamoeba castellanii develop central nervous system autoimmunity through the generation of cross-reactive T cells for myelin antigens

Chandirasegaran Massilamany, Francine Marciano-Cabral, Bruno da Rocha-Azevedo, Melissa Jamerson, Arunakumar Gangaplara, David Steffen, Rana Zabad, Zsolt Illes, Raymond A Sobel, Jay Reddy

Research output: Contribution to journalJournal articleResearchpeer-review

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.

Original languageEnglish
JournalP L o S One
Volume9
Issue number5
Pages (from-to)e98506
ISSN1932-6203
DOIs
Publication statusPublished - 2014

    Fingerprint

Cite this

Massilamany, C., Marciano-Cabral, F., Rocha-Azevedo, B. D., Jamerson, M., Gangaplara, A., Steffen, D., Zabad, R., Illes, Z., Sobel, R. A., & Reddy, J. (2014). SJL mice infected with Acanthamoeba castellanii develop central nervous system autoimmunity through the generation of cross-reactive T cells for myelin antigens. P L o S One, 9(5), e98506. https://doi.org/10.1371/journal.pone.0098506