TY  - JOUR
A1  - Solbach, W.
A1  - Bogdan, C.
A1  - Moll, Heidrun
A1  - Lohoff, M.
A1  - Röllinghoff, M.
T1  - Parasitäre Evasionsmechanismen: Beispiel Leishmanien
T1  - Mechanisms of Parasite Evasion: Leishmania as an Example
N2  - Leishmanien besitzen eine Vielzahl von Mechanismen, die humorale und zelluläre Immunabwehr effektiv zu unterlaufen. Diese hängen eng mit der Expression von hauptsächlich zwei Glykokonjugaten auf der Parasitenoberfläche zusammen, dem gp63 und dem Lipophosphoglykan. Die Parasiten sind einerseits schlechte Aktivatoren des alternativen Komplementweges und umgehen damit ihre eigene extrazelluläre Lyse. Oberflächengebundene Komplementfaktoren fördern andererseits die Aufnahme der Leishmanien durch Makrophagen. Solange diese nicht durch T-Zellen aktiviert sind, dienen sie den Parasiten als "Refugium". Dies gilt insbesondere, als Leishmanien in der Lage sind, 1. den "oxidative burst" zu hemmen; 2. toxische Sauerstoffmetaboliten zu entgiften; 3. abbauende lysosomale Enzyme zu hemmen und 4. das saure Milieu in den Lysosomen für ihren eigenen Metabolismus auszunutzen. Schließlich unterlaufen Leishmanien die zelluläre Immunabwehr des Wirts, indem sie die Aktivierung von T-Lymphozyten hemmen und die Expansion von T-Zell-Sub-populationen bewirken, die für ihr eigenes Überleben nützlich sind.
N2  - Leishmania display a variety of mechanisms for effective evasion of the humoral and cellular immune responses of the host which are strongly associ-ated with the expression of two major surface glycoconjugates, gp63 and lipophosphoglycan. The parasites are poor activators of the alternative com-plement pathway thus avoiding their own extracellular lysis. Complement bound on the surface of promastigotes promotes the uptake of leishmania by macrophages which function as »safe targets« as long as they are not acti-vated by T lymphocytes. This is due to the fact that intracellular parasites are able to 1. decrease the oxidative burst; 2. scavenge toxic oxygen metabolites; 3. inhibit degradative lysosomal enzymes; 4. exploit the acidic milieu of lysosomes for their own metabolism. Finally, leishmania have been shown to evade the host's cellular immune response by down-regulating T cell-activat-ing processes and by initiating the expansion of T cell subpopulations which promote their own survival.
KW  - Leishmanien
KW  - Immunsystem
KW  - Evasionsmechanismen
KW  - Makrophagen
KW  - T-Zellen
KW  - leishmania
KW  - immune System
KW  - evasion mechanisms
KW  - macrophages
KW  - T cells
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-30920
ER  - 
TY  - JOUR
A1  - Schleicher, Ulrike
A1  - Paduch, Katrin
A1  - Debus, Andrea
A1  - Obermeyer, Stephanie
A1  - König, Till
A1  - Kling, Jessica C.
A1  - Ribechini, Eliana
A1  - Dudziak, Diana
A1  - Mougiakakos, Dimitrios
A1  - Murray, Peter J.
A1  - Ostuni, Renato
A1  - Körner, Heinrich
A1  - Bogdan, Christian
T1  - TNF-Mediated Restriction of Arginase 1 Expression in Myeloid Cells Triggers Type 2 NO Synthase Activity at the Site of Infection
JF  - Cell Reports
N2  - Neutralization or deletion of tumor necrosis factor (TNF) causes loss of control of intracellular pathogens in mice and humans, but the underlying mechanisms are incompletely understood. Here, we found that TNF antagonized alternative activation of macrophages and dendritic cells by IL-4. TNF inhibited IL-4-induced arginase 1 (Arg1) expression by decreasing histone acetylation, without affecting STAT6 phosphorylation and nuclear translocation. In Leishmania major-infected C57BL/6 wild-type mice, type 2 nitric oxide (NO) synthase (NOS2) was detected in inflammatory dendritic cells or macrophages, some of which co-expressed Arg1. In TNF-deficient mice, Arg1 was hyperexpressed, causing an impaired production of NO in situ. A similar phenotype was seen in L. major-infected BALB/c mice. Arg1 deletion in hematopoietic cells protected these mice from an otherwise lethal disease, although their disease-mediating T cell response (Th2, Treg) was maintained. Thus, deletion or TNF-mediated restriction of Arg1 unleashes the production of NO by NOS2, which is critical for pathogen control.
KW  - TNF
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164897
VL  - 15
IS  - 5
ER  -