Complement C3 is required for the progression of cutaneous lesions and neutrophil attraction in Leishmania major infection.
To elucidate the role of complement-mediated uptake in Leishmania major infection in vivo, transgenic BALB/c mice that express the cobra venom factor (CVF) under control of the alpha1-antitrypsin promoter were infected. CVF expression in these mice leads to a continuous activation and subsequent consumption of complement C3 in the serum. In contrast to susceptible non-transgenic BALB/c mice, CVF-transgenic mice are highly resistant to L. major infection and show a significantly reduced parasite dissemination. Transient depletion of C3 in wild-type BALB/c mice delays progression of lesions for some days. Both CVF-transgenic and non-transgenic mice exhibit similar T cell responses upon infection. However, in CVF-transgenic mice, no infiltration of neutrophils, which were the prominent infiltrating cells at the site of infection in normal susceptible mice, could be detected. We conclude that C3 cleavage is required for the attraction of neutrophils that participate in parasite dissemination.
Jacobs
Thomas
T
Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, 20359, Hamburg, Germany. tjacobs@bni-hamburg.de
Andrä
Jörg
J
Gaworski
Iris
I
Graefe
Sebastian
S
Mellenthin
Katja
K
Krömer
Manfred
M
Halter
Roman
R
Borlak
Jürgen
J
Clos
Joachim
J
D000818:Animals; D003167:Complement Activation; D003176:Complement C3 / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000235:genetics / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D007962:Leukocytes / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration; D013601:T-Lymphocytes / Q000276:immunology
D003176:Complement C3; D004546:Elapid Venoms; C016310:cobra venom factor