The developmental hierarchy and scarcity of replicative slender trypanosomes in blood challenges their role in infection maintenance.
Proc Natl Acad Sci U S A
; 120(42): e2306848120, 2023 10 17.
Article
em En
| MEDLINE
| ID: mdl-37824530
ABSTRACT
The development of Trypanosoma brucei in its mammalian host is marked by a distinct morphological change as replicative "slender" forms differentiate into cell cycle arrested "stumpy" forms in a quorum-sensing-dependent manner. Although stumpy forms dominate chronic infections at the population level, the proportion of replicative parasites at the individual cell level and the irreversibility of arrest in the bloodstream are unclear. Here, we experimentally demonstrate that developmental cell cycle arrest is definitively irreversible in acute and chronic infections in mice. Furthermore, analysis of replicative capacity and single-cell transcriptome profiling reveal a temporal hierarchy, whereby cell cycle arrest and appearance of a reversible stumpy-like transcriptome precede irreversible commitment and morphological change. Unexpectedly, we show that proliferating parasites are exceptionally scarce in the blood after infections are established. This challenges the ability of bloodstream trypanosomes to sustain infection by proliferation or antigenic variation, these parasites instead being overwhelmingly adapted for transmission.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trypanosoma
/
Trypanosoma brucei brucei
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Reino Unido