A new model for elephantiasis

Elephantiasis Many organisms are able to adapt their development to the severity of their environment based on specific cues, and we have identified such a phenomenon, termed phenotypic plasticity, in the filarial parasite Litomosoides sigmodontis. Filarial nematodes infect about 200 million people worldwide, and much effort is going into finding a vaccine that would complement current drug treatments. Although anti-filarial immunity can be achieved, we show, in accord with evolutionary theory, that when these parasites infect a new host, they are able to adjust their development and reproduction to the presence of immune cells specialized in anti-helminth attack. These developmental schedules are determined within hours and impact their lifelong reproductive strategy; when immune attack is strong, and thus mortality is likely to be high, they produce offspring earlier and in greater numbers. Because current experimental vaccines rely on the very immune elements to which these nematodes adjust their development, their phenotypic plasticity could mitigate the expected reduction of disease burden in vaccinated populations.

Filarial Parasites Develop Faster and Reproduce Earlier in Response to Host Immune Effectors That Determine Filarial Life Expectancy. (2010) PLoS Biol 8(10): e1000525. doi:10.1371/journal.pbio.1000525
Humans and other mammals mount vigorous immune assaults against helminth parasites, yet there are intriguing reports that the immune response can enhance rather than impair parasite development. It has been hypothesized that helminths, like many free-living organisms, should optimize their development and reproduction in response to cues predicting future life expectancy. However, immune-dependant development by helminth parasites has so far eluded such evolutionary explanation. By manipulating various arms of the immune response of experimental hosts, we show that filarial nematodes, the parasites responsible for debilitating diseases in humans like river blindness and elephantiasis, accelerate their development in response to the IL-5 driven eosinophilia they encounter when infecting a host. Consequently they produce microfilariae, their transmission stages, earlier and in greater numbers. Eosinophilia is a primary host determinant of filarial life expectancy, operating both at larval and at late adult stages in anatomically and temporally separate locations, and is implicated in vaccine-mediated protection. Filarial nematodes are therefore able to adjust their reproductive schedules in response to an environmental predictor of their probability of survival, as proposed by evolutionary theory, thereby mitigating the effects of the immune attack to which helminths are most susceptible. Enhancing protective immunity against filarial nematodes, for example through vaccination, may be less effective at reducing transmission than would be expected and may, at worst, lead to increased transmission and, hence, pathology.

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