NIAID Scientists Make Major Advancement in Understanding of Parasite-Vector-Host Interaction
It’s a finding perfect for spooky season—inside a bloodsucking insect, a parasite uses the blood of mammals to get more fit to infect unsuspecting people. In this case, the story is more troubling because it’s a real threat. The parasite is Leishmania, which causes leishmaniasis, a primarily tropical and subtropical disease that can cause skin lesions and organ damage, and can be fatal. The bloodsucking insect that spreads Leishmania parasites is the sand fly, a small, biting vector that infects humans and other mammals with the parasite. Researchers at the National Institute of Allergy and Infectious Diseases (NIAID) found that the parasite uses antibodies from the human or mammalian host to form mating clumps in the sand fly gut, prompting a process that allows the parasite to adapt and become more suited to infecting people. The findings were published in Nature on October 25.
Leishmaniasis affects people in dozens of countries around the world. In the U.S., a few cases have been reported in Texas and Oklahoma. Different species of the Leishmania parasite can cause different types and symptoms of the disease. Cutaneous leishmaniasis is the most common form, which can cause skin lesions, sometimes resulting in permanent scarring. Visceral leishmaniasis affects the spleen, liver, bone marrow and other parts of the body, and severe cases can be fatal if untreated. Worldwide, it’s estimated that millions of people live with Leishmania infection, which can occur without symptoms, and the disease results in 30,000 to 50,000 deaths and over 1 million new cases per year. Despite the large toll leishmaniasis places on global human health, with low- and middle-income countries bearing the greatest burden, more research is needed to understand the Leishmania parasite to help eliminate the threat of this disease.
Leishmania can’t survive on its own. The parasite has a complex lifecycle where it completes some stages in a human or mammal host, and other stages in the sand fly vector. Much of the time, the single-celled parasite makes new cells as copies of itself. This process is efficient, but it isn’t a fast way to get new genes that can help the parasite spread faster. New genes can be obtained when two Leishmania cells form a hybrid and swap genes, a process called genetic exchange. Prior to the newly published study, the initiation of this process was not well understood.
In the new study, the researchers studied different Leishmania species and found that genetic exchange occurs in Leishmania mating clumps (LMCs). The LMCs were shown to form in the gut of the sand fly after it has taken a blood meal. The scientists also found that specific antibodies, called IgM natural antibodies (IgMn), from the human or mammalian host were necessary to prompt the parasite cells to form LMCs. The formation of LMCs and the genetic exchange—also referred to as mating—that occurs within them was confirmed in several ways. In one set of experiments, uninfected sand flies fed on Leishmania-infected mice, becoming infected with the parasite. The sand flies later fed on uninfected mice, and this blood meal, which contained IgMn, prompted formation of LMCs. In a control group, no LMCs formed in sand flies given blood that did not contain IgMn. This result, combined with extensive testing to eliminate other possibilities, confirmed that the parasite uses IgMn to initiate LMCs where genes are exchanged.
These findings represent a breakthrough in the understanding of parasite-vector-host interactions, as well as a unique example of how a parasite can evolve to exploit the machinery of its host for survival. Using IgMn to promote parasite mating in the insect vector seems particularly diabolical—the host’s immune system is co-opted to increase the fitness of the parasite, turning the defenses of the host into a weakness. But another turnabout may be coming—these findings could be key to discovering interventions to fight back against Leishmania.
Reference: Serafim, TD et al. Leishmania genetic exchange is mediated by IgM natural antibodies. Nature. https://doi.org/10.1038/s41586-023-06655-8 (2023).