title: The Trypanosoma cruzi flagellum is discarded via asymmetric cell division following invasion and provides early targets for protective CD8⁺ T cells.
abstract: During invasion of host cells by Trypanosoma cruzi, the parasite that causes Chagas disease, the elongated, flagellated trypomastigotes remodel into oval amastigotes with no external flagellum. The underlying mechanism of this remodeling and the fate of the flagellum are obscure. We discovered that T. cruzi trypomastigotes discard their flagella via an asymmetric cellular division. The flagellar proteins liberated become among the earliest parasite proteins to enter the MHC-I processing pathway in infected cells. Indeed, paraflagellar rod protein PAR4-specific CD8(+) T cells detect infected host cells >20 hr earlier than immunodominant trans-sialidase-specific T cells. Overexpression of PAR4 in T. cruzi enhanced the subdominant PAR4-specific CD8(+) T cell response, resulting in improved control of a challenge infection. These results provide insights into previously unappreciated events in intracellular invasion by T. cruzi and highlight the importance of T cells that recognize infected host cells early in the infectious process, in the control of infections.
authors.affiliation: Department of Cellular Biology and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30602, USA.
authors.forename: Samarchith P
authors.initials: SP
authors.lastname: Kurup
authors.affiliation: Department of Cellular Biology and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30602, USA. Electronic address: tarleton@uga.edu.
authors.forename: Rick L
authors.initials: RL
authors.lastname: Tarleton
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D014355:Chagas Disease / Q000276:immunology / Q000469:parasitology; D004195:Disease Models, Animal; D005407:Flagella / Q000276:immunology*; D008810:Mice, Inbred C57BL; D015800:Protozoan Proteins / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000502:physiology*
chemical_list: D015800:Protozoan Proteins