Complement C3 is required for the progression of cutaneous lesions and neutrophil attraction in Leishmania major infection

Abstract

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.

IL-17 Promotes Progression of Cutaneous Leishmaniasis in Susceptible Mice

“…Although neutrophils are among the first cells recruited to L. major lesions and neutrophils have been shown to play some role in inducing protection (33, 34), several reports previously demonstrated that persistent inflammation characterized by increased neutrophil infiltration promoted disease susceptibility in BALB/c mice (16, 17, 35). Increased numbers of neutrophils were identified in established lesions in susceptible mice as compared to those of genetically resistant animals (36, 37).…”

The clinical value of neutrophil extracellular traps

“…PTX3 binding of C1q results in activation of the classical complement pathway. The formation of the C1 complex and of antigen-immune complexes entails increased phagocytic activity of monocytes and macrophages, secretion of immunoglobulins by B lymphocytes, stimulation of oxidative metabolism in neutrophils, adhesion of immune complexes to endothelial cells, and increased clearance of apoptotic cells [25]. Like histones, pentraxin co-localized to NETs seems to be a central molecule in promoting local antimicrobial immune responses [8].…”

The Prominent Role of Neutrophils during the Initial Phase of Infection byLeishmaniaParasites

“…Upon infection, these mice did not develop any inflammatory lesions and had lower neutrophil infiltration at the site of infection [34]. It remains difficult to assess if such decreased neutrophil recruitment is the cause or the result of the observed inhibition of lesion development.…”