TY  - JOUR
A1  - Nono, Justin Komguep
A1  - Pletinckx, Katrien
A1  - Lutz, Manfred B.
A1  - Brehm, Klaus
T1  - Excretory/Secretory-Products of Echinococcus multilocularis Larvae Induce Apoptosis and Tolerogenic Properties in Dendritic Cells In Vitro
JF  - PLoS Neglected Tropical Diseases
N2  - Background: Alveolar echinococcosis, caused by Echinococcus multilocularis larvae, is a chronic disease associated with considerable modulation of the host immune response. Dendritic cells (DC) are key effectors in shaping the immune response and among the first cells encountered by the parasite during an infection. Although it is assumed that E. multilocularis, by excretory/secretory (E/S)-products, specifically affects DC to deviate immune responses, little information is available on the molecular nature of respective E/S-products and their mode of action. Methodology/Principal Findings: We established cultivation systems for exposing DC to live material from early (oncosphere), chronic (metacestode) and late (protoscolex) infectious stages. When co-incubated with Echinococcus primary cells, representing the invading oncosphere, or metacestode vesicles, a significant proportion of DC underwent apoptosis and the surviving DC failed to mature. In contrast, DC exposed to protoscoleces upregulated maturation markers and did not undergo apoptosis. After pre-incubation with primary cells and metacestode vesicles, DC showed a strongly impaired ability to be activated by the TLR ligand LPS, which was not observed in DC pre-treated with protoscolex E/S-products. While none of the larvae induced the secretion of pro-inflammatory IL-12p70, the production of immunosuppressive IL-10 was elevated in response to primary cell E/S-products. Finally, upon incubation with DC and naive T-cells, E/S-products from metacestode vesicles led to a significant expansion of Foxp3+ T cells in vitro. Conclusions: This is the first report on the induction of apoptosis in DC by cestode E/S-products. Our data indicate that the early infective stage of E. multilocularis is a strong inducer of tolerance in DC, which is most probably important for generating an immunosuppressive environment at an infection phase in which the parasite is highly vulnerable to host attacks. The induction of CD4+CD25+Foxp3+ T cells through metacestode E/S-products suggests that these cells fulfill an important role for parasite persistence during chronic echinococcosis.
KW  - granulosus
KW  - hydatid disease
KW  - metacestode vesicles
KW  - antigen-B
KW  - alveoar echinococcosis
KW  - TGF-BETA
KW  - regulatory T cells
KW  - gene expression
KW  - Brugia Malayi
KW  - TNF-alpha
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134280
VL  - 6
IS  - 2
ER  - 
TY  - JOUR
A1  - Kühlhorn, Franziska
A1  - Rath, Matthias
A1  - Schmoeckel, Katrin
A1  - Cziupka, Katharina
A1  - Nguyen, Huu Hung
A1  - Hildebrandt, Petra
A1  - Hünig, Thomas
A1  - Sparwasser, Tim
A1  - Huehn, Jochen
A1  - Pötschke, Christian
A1  - Bröker, Barbara M.
T1  - \(Foxp3^+\) Regulatory T Cells Are Required for Recovery from Severe Sepsis
JF  - PLoS ONE
N2  - The role of regulatory T cells (Tregs) in bacterial sepsis remains controversial because antibody-mediated depletion experiments gave conflicting results. We employed DEREG mice (DEpletion of REGulatory T cells) and a caecal ligation and puncture model to elucidate the role of \(CD4^+Foxp3^+\) Tregs in sepsis. In DEREG mice natural Tregs can be visualized easily and selectively depleted by diphtheria toxin because the animals express the diphtheria toxin receptor and enhanced green fluorescent protein as a fusion protein under the control of the foxp3 locus. We confirmed rapid Treg-activation and an increased ratio of Tregs to Teffs in sepsis. Nevertheless, 24 h after sepsis induction, Treg-depleted and control mice showed equally strong inflammation, immune cell immigration into the peritoneum and bacterial dissemination. During the first 36 h of disease survival was not influenced by Treg-depletion. Later, however, only Treg-competent animals recovered from the insult. We conclude that the suppressive capacity of Tregs is not sufficient to control overwhelming inflammation and early mortality, but is a prerequisite for the recovery from severe sepsis.
KW  - CD4(+)CD25(+)
KW  - toll-like receptors
KW  - TGF-BETA
KW  - mediated suppression
KW  - polymicrobial sepsis
KW  - improves survival
KW  - adoptive transfer
KW  - infected mice
KW  - in-vivo
KW  - CD4(+)
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130940
VL  - 8
IS  - 5
ER  -