CD4 + T Cell-Dependent Macrophage Activation Modulates Sustained PS Exposure on Intracellular Amastigotes of Leishmania amazonensis

Joao Luiz Mendes Wanderley, Poliana Deolindo, Eric Carlsen, Arieli Bernardo Portugal, Renato Augusto DaMatta, Marcello Andre Barcinski, Lynn Soong

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Leishmania amazonensis amastigotes can make use of surface-exposed phosphatidylserine (PS) molecules to promote infection and non-classical activation of macrophages (MΦ), leading to uncontrolled intracellular proliferation of the parasites. This mechanism was quoted as apoptotic mimicry. Moreover, the amount of PS molecules exposed on the surface of amastigotes correlates with the susceptibility of the host. In this study, we tested whether host cellular responses influence PS expression on intracellular amastigotes. We found that the level of PS exposure on intracellular amastigotes was modulated by CD4+ T cell and MΦ activation status in vitro and in vivo. L. amazonensis infection generated a Th1/Th2-mixed cytokine profile, providing the optimal MΦ stimulation that favored PS exposure on intracellular amastigotes. Maintenance of PS exposed on the parasite was dependent on low, but sustained, levels of nitric oxide and polyamine production. Amastigotes obtained from lymphopenic nude mice did not expose PS on their surface, and adoptive transfer of CD4+ T cells reversed this phenotype. In addition, histopathological analysis of mice treated with anti-PS antibodies showed increased inflammation and similarities to nude mouse lesions. Collectively, our data confirm the role of pathogenic CD4+ T cells for disease progression and point to PS as a critical parasite strategy to subvert host immune responses.

Original languageEnglish (US)
Number of pages1
JournalFrontiers in Cellular and Infection Microbiology
Volume9
DOIs
StatePublished - Jan 1 2019

Fingerprint

Macrophage Activation
Leishmania
Phosphatidylserines
T-Lymphocytes
Parasites
Nude Mice
Adoptive Transfer
Polyamines
Infection
Disease Progression
Anti-Idiotypic Antibodies
Nitric Oxide
Maintenance
Cytokines
Inflammation
Phenotype

Keywords

  • amastigote
  • immune evasion
  • macrophage
  • parasitophorous vacuole
  • phosphatidylserine
  • T cell

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

Cite this

CD4 + T Cell-Dependent Macrophage Activation Modulates Sustained PS Exposure on Intracellular Amastigotes of Leishmania amazonensis . / Wanderley, Joao Luiz Mendes; Deolindo, Poliana; Carlsen, Eric; Portugal, Arieli Bernardo; DaMatta, Renato Augusto; Barcinski, Marcello Andre; Soong, Lynn.

In: Frontiers in Cellular and Infection Microbiology, Vol. 9, 01.01.2019.

Research output: Contribution to journalArticle

Wanderley, Joao Luiz Mendes ; Deolindo, Poliana ; Carlsen, Eric ; Portugal, Arieli Bernardo ; DaMatta, Renato Augusto ; Barcinski, Marcello Andre ; Soong, Lynn. / CD4 + T Cell-Dependent Macrophage Activation Modulates Sustained PS Exposure on Intracellular Amastigotes of Leishmania amazonensis In: Frontiers in Cellular and Infection Microbiology. 2019 ; Vol. 9.
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