Brugia malayi microfilaraemia in mice: a model for the study of the host response to microfilariae

Abstract

SUMMARYMicrofilariae of Brugia malayi were obtained from the peritoneal cavities of infected gerbils and were then injected intravenously into mice. A sub-periodic, nocturnal microfilaraemia was produced. The level of microfilaraemia was proportional to the number of parasites injected, with approximately 1–3% of microfilariae being found in the peripheral circulation. The duration of microfilaraemia was proportional to the number of parasites injected; it subsided by 30 days after injection of 104 microfilariae but was still present at a low level 120 days after injection of 2 × 105 microfilariae. A transient splenomegaly developed after injection of microfilariae. Histopathological examination revealed large numbers of microfilariae free in the lumens of pulmonary small blood vessels and without any accompanying inflammatory reaction. Lesser numbers of microfilariae were seen in the cardiac blood and hepatic and renal blood vessels for the first few days after injection. There was cellular proliferation in the splenic white pulp and vascular congestion of the red pulp. Microfilariae labelled with 51Cr were injected intravenously; 57% of radioactivity was found in the lungs, 8·5% in the liver and 2·9% in the spleen. Mice developed immediate hypersensitivity reactions to B. malayi antigen by 4 weeks after injection, but Arthus and delayed hypersensitivity reactions were not seen at any time. When mice which had been injected 5 months previously were challenged with a 2nd injection of microfilariae, there was an accelerated clearance of parasites over 2 weeks and a marked peripheral blood eosinophilia developed. In contrast with natural infections, in which the continuous production of microfilariae complicates assessment, this model provides a system in which factors controlling the circulation of microfilariae in the bloodstream can be studied independently.

Differential recognition of a protective filarial antigen by antibodies from humans with bancroftian filariasis.

“…This protective response (manifest by a >80% decrease in microfilaremia and 50% reduction in adult female worm burden) was associated with development of jird antibodies to antigens having apparent molecular weights similar to those recognized by mice and rabbits. In the present study, we compared the efficacy of the four major mf molecules in inducing resistance against microfilaremia in mice, experimental animals in which studies of antibody-dependent host clearance mechanisms directed exclusively against this stage of the parasite life cycle are possible (13,22). Whereas mice immunized with gel slices containing the 112,000-, 60,000-, or 45,000-Mr antigens did not have a significantly lower level of parasitemia compared with controls, recipients of the -25,000-M, antigen showed a 78-99% reduction in microfilaremia.…”

“…The injections were repeated in 2 wk and the animals challenged intravenously with I05 live mf 2 wk later. The level and duration of microfilaremia were determined as previously described (22).…”

Clearance of Brugia pahangi microfilariae in immunized mice

“…The usefulness of the murine microfilaraemia model has been emphasized (7,8) for exploring anti-Mf responses in mice, although these hosts are not permissive to infection with third stages of Brugia filariae. In the absence of suitable laboratory hosts, the murine models are useful to study the mechanisms of immunity against filarial parasites and to monitor relevant antifilarial responses under controlled conditions.…”

“…Commercial availability of various genetically defined murine strains and their well characterized immunological reagents made them suitable for protective immunity experiments (2). Grove et al (7) and Kazura and Davies (8) employed mice successfully for inducing B. malayi micro-filaraemia. A high degree of protective immunity directed against microfilariae (Mf) was demonstrated which is mediated by antibody and effector cells.…”

Brugia malayi microfilariae adhere to human vascular endothelial cells in a C3-dependent manner

“…Indeed, the synchronisation of microfilarial appearance in the blood with the peak feeding time of the local mosquito vector population in different parts of the world, suggests a co-evolutionary adaptation for maximising parasite transmission [1,2,3]. It is known that Mf, when they are not in the peripheral blood, generally sequester in the lung capillaries of the host [4,5,6]. However, there has been limited insight into the underlying mechanism of this pulmonary sequestration.…”