Modulation of the immune and inflammatory responses by plasmodium falciparum schizont extracts: Role of myeloid dendritic cells in effector and regulatory functions of CD4+ lymphocytes

Ann Maria Clemente, Giulia Fadigati, Roberto Caporale, Damiano G. Marchese, Giuseppe Castronovo, Anna Rosa Sannell, Carlo Severini, Federica Verra, Enrico Garaci, Federico Cozzolino, Maria Gabriella Torcia

Research output: Contribution to journalArticle

Abstract

The optimal immune response to malaria infection comprises rapid induction of inflammatory responses promptly counteracted by regulatory mechanisms to prevent immunopathology. To evaluate the role of dendritic cells (DC) in the balance of parasite-induced inflammatory/anti-inflammatory mechanisms, we studied the activity of monocyte-derived dendritic cells (MDDC), previously exposed to soluble extracts of Plasmodium falciparum-infected red blood cells (PfSE), in the differentiation of CD4 cells isolated from donors never exposed to malaria infection. We show that MDDC exposed to PfSE are extremely efficient to induce a contemporary differentiation of TH1 effector cells and T regulatory (Treg) cells in CD4 T cells even when exposed to low concentrations of parasitic extracts. Treg cells induced by MDDC infected with PfSE (MDDC-PfSE) produce transforming growth factor beta (TGF-α) and interleukin 10 (IL-10) and are endowed with strong suppressive properties. They also show phenotypical and functional peculiarities, such as the contemporary expression of markers of Treg and TH1 differentiation and higher sensitivity to TLR4 ligands both inducing an increasing production of suppressive cytokines. On the whole, our data indicate that MDDC exposed to PfSE orchestrate a well-balanced immune response with timely differentiation of TH1 and Treg cells in CD4 cells from nonimmune donors and suggest that, during the infection, the role of MDCC could be particularly relevant in low-parasitemia conditions.

Original languageEnglish
Pages (from-to)1842-1851
Number of pages10
JournalInfection and Immunity
Volume81
Issue number5
DOIs
Publication statusPublished - May 2013

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Modulation of the immune and inflammatory responses by plasmodium falciparum schizont extracts: Role of myeloid dendritic cells in effector and regulatory functions of CD4+ lymphocytes'. Together they form a unique fingerprint.

  • Cite this

    Clemente, A. M., Fadigati, G., Caporale, R., Marchese, D. G., Castronovo, G., Sannell, A. R., Severini, C., Verra, F., Garaci, E., Cozzolino, F., & Torcia, M. G. (2013). Modulation of the immune and inflammatory responses by plasmodium falciparum schizont extracts: Role of myeloid dendritic cells in effector and regulatory functions of CD4+ lymphocytes. Infection and Immunity, 81(5), 1842-1851. https://doi.org/10.1128/IAI.01226-12