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 language | English |
|---|---|
| Pages (from-to) | 1842-1851 |
| Number of pages | 10 |
| Journal | Infection and Immunity |
| Volume | 81 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2013 |
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ASJC Scopus subject areas
- Immunology
- Microbiology
- Parasitology
- Infectious Diseases
Cite this
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. / Clemente, Ann Maria; Fadigati, Giulia; Caporale, Roberto; Marchese, Damiano G.; Castronovo, Giuseppe; Sannell, Anna Rosa; Severini, Carlo; Verra, Federica; Garaci, Enrico; Cozzolino, Federico; Torcia, Maria Gabriella.
In: Infection and Immunity, Vol. 81, No. 5, 05.2013, p. 1842-1851.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Modulation of the immune and inflammatory responses by plasmodium falciparum schizont extracts
T2 - Role of myeloid dendritic cells in effector and regulatory functions of CD4+ lymphocytes
AU - Clemente, Ann Maria
AU - Fadigati, Giulia
AU - Caporale, Roberto
AU - Marchese, Damiano G.
AU - Castronovo, Giuseppe
AU - Sannell, Anna Rosa
AU - Severini, Carlo
AU - Verra, Federica
AU - Garaci, Enrico
AU - Cozzolino, Federico
AU - Torcia, Maria Gabriella
PY - 2013/5
Y1 - 2013/5
N2 - 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.
AB - 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.
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U2 - 10.1128/IAI.01226-12
DO - 10.1128/IAI.01226-12
M3 - Article
VL - 81
SP - 1842
EP - 1851
JO - Infection and Immunity
JF - Infection and Immunity
SN - 0019-9567
IS - 5
ER -