GHTM

Global Health and Tropical Medicine

  • GHTM
    • Vision
    • Mission
    • Governance
    • Scientific Advisory Board
  • News
    • Outreach
    • Events
      • GHTM Sessions
      • Workshops
    • Articles
    • Jobs
  • Research
    • Cross-cutting issues
      • Global Pathogen Dispersion and Population Mobility
      • Drug Discovery and Drug Resistance
      • Diagnostics
      • Public Health Information
      • Fair Research Partnerships
    • Research Groups
      • PPS – Population health, policies and services
      • THOP – TB, HIV and opportunistic diseases and pathogens
      • VBD – Vector borne diseases and pathogens
      • IHC – Individual health care
    • Research in numbers
      • 2020
      • 2019
      • 2018
      • 2017
    • Projects
      • Ongoing Projects
    • Members
      • Population health, policies and services
        • PPS PhD members
        • PPS non PhD members
      • TB, HIV and opportunistic diseases and pathogens
        • THOP PhD members
        • THOP non PhD members
      • Vector-borne diseases and pathogens
        • VBD PhD members
        • VBD non PhD members
      • Individual Health Care
        • IHC PhD members
        • IHC non PhD members
      • Technical / administrative support
  • Publications
  • Education
    • Master Theses
    • PhD Theses
  • Services
Home / Publicações / Role of the inhibitor of serine peptidase 2 (ISP2) of Trypanosoma brucei rhodesiense in parasite virulence and modulation of the inflammatory responses of the host

Role of the inhibitor of serine peptidase 2 (ISP2) of Trypanosoma brucei rhodesiense in parasite virulence and modulation of the inflammatory responses of the host

  • Autores: David Jessula Levy, Amy Goundry, Raquel S S Laires, Tatiana F R Costa, Carlos Mendes Novo, Dennis J Grab, Jeremy C Mottram, Ana Paula C A Lima
  • Ano de Publicação: 2021
  • Journal: Plos Neglected Tropical Diseases, 15(6), art e0009526
  • Link: https://doi.org/10.1371/journal.pntd.0009526

ABSTRACT

Trypanosoma brucei rhodesiense is one of the causative agents of Human African Trypanosomiasis (HAT), known as sleeping sickness. The parasite invades the central nervous system and causes severe encephalitis that is fatal if left untreated. We have previously identified ecotin-like inhibitors of serine peptidases, named ISPs, in trypanosomatid parasitic protozoa. Here, we investigated the role of ISP2 in bloodstream form T. b. rhodesiense. We generated gene-deficient mutants lacking ISP2 (Δisp2), which displayed a growth profile in vitro similar to that of wild-type (WT) parasites. C57BL/6 mice infected with Δisp2 displayed lower blood parasitemia, a delayed hind leg pathological phenotype and survived longer. The immune response was examined at two time-points that corresponded with two peaks of parasitemia. At 4 days, the spleens of Δisp2-infected mice had a greater percentage of NOS2+ myeloid cells, IFN-γ+-NK cells and increased TNF-α compared to those infected with WT and parasites re-expressing ISP2 (Δisp2:ISP2). By 13 days the increased NOS2+ population was sustained in Δisp2-infected mice, along with increased percentages of monocyte-derived dendritic cells, as well as CD19+ B lymphocytes, and CD8+ and CD4+ T lymphocytes. Taken together, these findings indicate that ISP2 contributes to T. b. rhodesiense virulence in mice and attenuates the inflammatory response during early infection.

 

AUTHOR SUMMARY

Trypanosoma brucei rhodesiense are protozoan parasites that cause deadly diseases in humans. The parasites are transmitted by the bite of infected tsetse flies and can penetrate the brain, causing severe inflammation, accompanied by motor disability, neurological disorders and death. It is important to understand how and which parasite factors contribute to infection in order to improve treatment alternatives. In their genome, these parasites have genes called ISPs similar to genes of bacteria, which encode proteins that inhibit serine peptidases of the trypsin family. Here, we studied the role of ISP2 in T. b. rhodesiense by analyzing parasite knock-out mutants for isp2 in experimental infections in mice. We found that ISP2 contributes to blood parasitemia, to the clinical signs of motor disability, and to reduce the levels of the inflammatory response of the host, therefore, contributing to infection.

 

KEYWORDS

Trypanosoma brucei; parasite; Trypanosomiasis; inhibitors of serine peptidases; ISPs; Africa; Human African Trypanosomiasis; sleeping sickness.

Share this:

  • Click to share on Facebook (Opens in new window)
  • Click to share on Twitter (Opens in new window)
  • Click to share on LinkedIn (Opens in new window)
  • Click to share on Pinterest (Opens in new window)
  • Click to share on WhatsApp (Opens in new window)
  • Click to print (Opens in new window)

Events

NOVA Sciencepreneur program: registration is open

  The Sciencepreneur ® program is aimed at NOVA scientists who are seeking to create value … [Read More...]

IHMT selected for the pilot phase of the Research Data Repository Service of the FCT

  In order to promote good practices in Open Science with regard to research data and … [Read More...]

Paulo Ferrinho interviewed for the new e-magazine of European and Developing Countries Clinical Trials Partnership (EDCTP)

Paulo Ferrinho, professor and Diretor of Public Global Health Departament at the Instituto de … [Read More...]

How can we improve the environmental performance of our laboratories?

  Every day in NOVA's laboratories research is carried out with the consumption of numerous … [Read More...]

Call for PhD Studentships

The Institute of Hygiene and Tropical Medicine (IHMT), Universidade Nova de Lisboa (NOVA), through … [Read More...]

IHMT | GHTM – APPLICATIONS ARE OPEN!

IHMT | GHTM - Applications are open for three research vacancies:   One position - PhD … [Read More...]

About GHTM

GHTM is a R&D Center that brings together researchers from IHMT with a track record in Tropical Medicine and International/Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

Contacts

Rua da Junqueira, 100
1349-008 Lisboa
Portugal
+351 213 652 600
+351 213 632 105

  • Facebook
  • YouTube

Subscribe Newsletter

  • How to get to GHTM/IHMT
  • GHTM Sessions
  • Research Groups
  • Cross-cutting issues
© Copyright 2023 IHMT-UNL Todos os Direitos Reservados.
  • Universidade Nova de Lisboa
  • Fundação para a Ciência e a Tecnologia

    Project UID/Multi/04413/2013