Loss of Complement Activation and Leukocyte Adherence asNippostrongylus brasiliensisDevelops within the Murine Host

Abstract

Complement activation and C3 deposition on the surface of parasitic helminths may be important for recruitment of leukocytes and for damage to the target organism via cell-mediated mechanisms. Inhibition of complement activation would therefore be advantageous to parasites, minimizing damage and enhancing migration through tissues. The aim of this study was to determine ex vivo if complement activation by, and leukocyte adherence to, the nematode Nippostrongylus brasiliensis change as the parasite matures and migrates through the murine host. Pathways of activation of complement and the mechanism of adherence of leukocytes were also defined using sera from mice genetically deficient in either C1q, factor B, C1q and factor B, C3, or C4. Substantive deposition of C3 and adherence of eosinophil-rich leukocytes were seen with infective-stage (L3) but not with lung-stage (L4) larvae. Adult intestinal worms had low to intermediate levels of both C3 and leukocyte binding. For L3 and adult worms, complement deposition was principally dependent on the alternative pathway. For lung-stage larvae, the small amount of C3 detected was dependent to similar degrees on both the lectin and alternative pathways. The classical pathway was not involved for any of the life stages of the parasite. These results suggest that in primary infections, the infective stage of N. brasiliensis is vulnerable to complement-dependent attack by leukocytes. However, within the first 24 h of infection, N. brasiliensis acquires the ability to largely avoid complement-dependent immune responses.

Regulation of Carcinogenesis by IL-5 and CCL11: A Potential Role for Eosinophils in Tumor Immune Surveillance

“…In addition, tumor-specific Abs may earmark tumor cells for killing by eosinophils via mechanisms similar to those demonstrated in studies of immunity to helminthic parasites (29). Our recent studies have demonstrated that migration of parasitic helminths in vivo can be impeded by eosinophils, and eosinophil attachment to larvae occurs rapidly and early in primary infections via complement C3 (30,31). However, at least in the Nippostrongylus brasiliensis parasitic model, Ab is not the main mechanism of recognition and attachment of eosinophils to helminth larvae (L. A. Dent, unpublished data).…”

Eosinophils Mediate Protective Immunity against Secondary Nematode Infection

“…IgE is denatured by heat and excluded from precipitates prepared by salt precipitation at 35% saturation. Complement has been shown to be important for immunity to parasitic infections (54-56), and T. spiralis NBL are potent activators of complement (57). Furthermore, mouse eosinophils express functional complement receptors (58).…”

Borrelia burgdorferiBinding of Host Complement Regulator Factor H Is Not Required for Efficient Mammalian Infection

“…The genotypes of these mice were initially confirmed by M. Botto, who developed the Cfh Ϫ/Ϫ strain, and then reconfirmed by M. E. Woodman following completion of these studies. Both the Cfh Ϫ/Ϫ and Bf Ϫ/Ϫ strains have been used extensively by others for a variety of infection and other studies (2,23,32,56,63,66,67,82,90,91). The Botto laboratory provided these mouse strains to the Stevenson and Wooten laboratories, where the experiments described herein were performed.…”