Human Leukocytes Kill Parasites that Cause Lymphatic Filariasis

Brugia malayi microfilaria
Attachment of human neutrophils and monocytes to Brugia malayi microfilaria precedes parasite killing

Adrian Wolstenholme and his collaborators at the University of Georgia have confirmed that leukocytes from uninfected people can recognize, attach to and kill the microfilariae stage of Brugia malayi in vitro(1).

What is Lymphatic Filariasis

Lymphatic filariasis is a disfiguring and debilitating neglected tropical diseases caused by filarial parasitic nematodes. Wuchereria bancrofti, Brugia malayi and Brugia timori infect over 100 million people worldwide. In addition to lymphatic filariasis, other closely related filarial parasites can also cause onchocerciasis (river blindness). Throughout history, parasitic nematode infections have had a major impact on human development, especially in the poorest and most disadvantaged populations.

A hallmark of the infection is that the parasite is long-living and produces a very large number of microfilariae. Adult worms live in the human lymphatic system (lymph nodes and vessels) and produce millions of microscopic worms, also known as microfilariae. The microfilariae circulate in the bloodstream and are taken up when a mosquito bites the person. In the mosquito, the microfilaria mature and the more mature larval worms are transmitted to another human during the second blood meal of the female mosquito. The larval worms then mature into adults, a process that can take up to 6 months, and adult worms can live 5 -7 years (CDC).

The parasites that cause lymphatic filariasis and onchocerciasis are found in the tropics and subtropics of Asia, Africa, the western Pacific and parts of the Caribbean and South America.

Fig. 6
Fig 6. Mf survival in the presence of human PMNs and monocytes.

Controlling and Eliminating Lymphatic Filariasis

The current strategy for eliminating lymphatic filariasis is through mass drug administration. Albendazole, ivermectin and diethylcarbamizne are used to target the microfilariae in the bloodstream. If microfilariae can be eliminated from the person, then transmission to mosquitoes is stopped and thus preventing future infections in humans.

Wolstenholme and his collaborators wanted to better understand the host-microfilariae interactions and the role a person’s innate immune system plays in filarial parasite defense and the regulation of microfilaremia, a key determinant of disease transmission.

Major Findings of the Study

The study shows that human peripheral blood innate immune cell populations can recognize, trap and kill the blood-circulating stage of the human filarial parasitic nematode Brugia malayi. Additionally, the complement specific inhibitor compstatin failed to have any biologically significant effects on either polymorphonuclear leukocyte attachments or leukocyte mediated microfilariae killing. Antibodies against CD11b and ICAM-1, two molecules previously implicated in the interactions between microfilariae and the immune system, also failed to inhibit killing, suggesting that they are not required for this process to take place.

Variation in worm killing and leukocyte attachment between human blood donors suggest that the innate immune system could significantly contribute to the regulation of host tolerance and susceptibility to infection and more specifically the regulation of microfilaremia which is a key determinant of human infection and the transmission of lymphatic filariasis.

About the Wolstenholme Research Group

Current research efforts within the Wolstenholme lab are focused on understanding complex interactions between the host’s immune system, the parasitic worm and anthelmintic drug treatments, which rapidly clear microfilariae from the host’s blood stream. It is hoped that these efforts could help better understand the mode of action of these widely administered drugs, and perhaps inform future treatment practices in a bid to increase the chances of eliminating this neglected tropical disease.

(1)McCoy CJ, Reaves BJ, Giguère S, Coates R, Rada B, Wolstenholme AJ (2017). Human Leukocytes Kill Brugia malayi Microfilariae Independently of DNA-Based Extracellular Trap Release. PLoS Negl Trop Di 1(1): e0005279. doi:10.137/journal.pntd.ooo5279 Read the full paper online

S1. Video capture of Mf tethered within PMN extruded extracellular DNA.