| Author | Costa, Tatiana F. R. | |
| Author | Goundry, Amy | |
| Author | Morrot, Alexandre | |
| Author | Grab, Dennis J. | |
| Author | Mottram, Jeremy C. | |
| Author | Lima, Ana Paula C. A. | |
| Access date | 2023-04-24T13:13:49Z | |
| Available date | 2023-04-24T13:13:49Z | |
| Document date | 2023 | |
| Citation | COSTA, Tatiana F. R. et al. Trypanosoma brucei rhodesiense Inhibitor of Cysteine Peptidase (ICP) Is Required for Virulence in Mice and to Attenuate the Inflammatory Response. International Journal o f Molecular Sciences, v.24, 656, p. 1 - 21, 2023. | en_US |
| ISSN | 1422-0067 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/57924 | |
| Language | eng | en_US |
| Publisher | MDPI | en_US |
| Rights | open access | |
| Subject in Portuguese | Inibidor | en_US |
| Subject in Portuguese | Chagasin | en_US |
| Subject in Portuguese | Inflamação | en_US |
| Subject in Portuguese | Trypanosoma | en_US |
| Subject in Portuguese | Virulência | en_US |
| Subject in Portuguese | Protease | en_US |
| Title | Trypanosoma brucei rhodesiense Inhibitor of Cysteine Peptidase (ICP) Is Required for Virulence in Mice and to Attenuate the Inflammatory Response | en_US |
| Type | Article | en_US |
| DOI | 10.3390/ijms24010656 | |
| Abstract | The protozoan Trypanosoma brucei rhodesiense causes Human African Trypanosomiasis,
also known as sleeping sickness, and penetrates the central nervous system, leading to meningoencephalitis.
The Cathepsin L-like cysteine peptidase of T. b. rhodesiense has been implicated in
parasite penetration of the blood–brain barrier and its activity is modulated by the chagasin-family
endogenous inhibitor of cysteine peptidases (ICP). To investigate the role of ICP in T. b. rhodesiense
bloodstream form, ICP-null (Dicp) mutants were generated, and lines re-expressing ICP (Dicp:ICP).
Lysates of Dicp displayed increased E-64-sensitive cysteine peptidase activity and the mutant parasites
traversed human brain microvascular endothelial cell (HBMEC) monolayers in vitro more
efficiently. Dicp induced E-selectin in HBMECs, leading to the adherence of higher numbers of human
neutrophils. In C57BL/6 mice, no Dicp parasites could be detected in the blood after 6 days, while
mice infected with wild-type (WT) or Dicp:ICP displayed high parasitemia, peaking at day 12. In
mice infected with Dicp, there was increased recruitment of monocytes to the site of inoculation and
higher levels of IFN- in the spleen. At day 14, mice infected with Dicp exhibited higher preservation
of the CD4+, CD8+, and CD19+ populations in the spleen, accompanied by sustained high IFN-
while NK1.1+ populations receded nearly to the levels of uninfected controls. We propose that ICP
helps to downregulate inflammatory responses that contribute to the control of infection. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofisica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofisica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz (FIOCRUZ). Centro de Pesquisa em Tuberculose. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. | en_US |
| Affilliation | York Biomedical Research Institute and Department of Biology, University of York, York YO10 5DD, UK. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofisica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | en_US |
| Subject | Inhibitor | en_US |
| Subject | Chagasin | en_US |
| Subject | Inflammation | en_US |
| Subject | Trypanosoma | en_US |
| Subject | Virulence | en_US |
| Subject | Protease | en_US |
