]: A colorized image of parasite clumps from a scanning electron microscope.
Researchers used a scanning electron microscope to visualize Leishmania parasite clumps (colorized).
Vinod Nair, Rose Perry-Gottschalk, and Ana Barletta

After sandflies feast on blood from a vertebrate host, Leishmania parasites mate and multiply within their guts. Leishmania mainly reproduces asexually but can fuse to form hybrids and swap genes between parasites.¹ However, factors that mediate genetic exchange are poorly understood. In a recent Nature paper, researchers reported that Leishmania uses vertebrate host antibodies from the sandflies’ blood meal to mate, unveiling a new paradigm in parasite-vector-host interactions.² 

Jesus Valenzuela, a biochemist at the National Institute of Allergy and Infectious Diseases, and his team cocultured two Leishmania strains in media containing sera from more than ten different vertebrates, including adult humans, to recapitulate the sandfly’s meal. They observed the formation of spherical Leishmania mating clumps (LMC), which facilitated genetic exchange, in all parasites except those cultured in the standard culture medium containing fetal bovine serum. 

When Valenzuela analyzed the different sera, he noted that they all contained IgM natural antibodies (IgMn). Without IgMn, the LMC failed to form. Further characterization showed that IgMn bound to Leishmania to facilitate fusion, genetic exchange, and eventual dissociation to release new parasites. 

“It’s an unexpected way to facilitate genetic exchange, but this work pinpointed these natural IgM antibodies as a critical factor,” said Nathan Peters, an immunologist at the University of Calgary who was not involved in the study. “It’s fascinating how the parasites use these defense mechanisms in their favor.”

Gene transcription analysis of the parasite clump revealed that IgMn upregulated proteins involved in cell fusion and division. The team also confirmed their findings in vivo by controlling the IgMn intake of sandflies. Sandflies on a consistent IgMn diet showed a 12-fold increase in LMC compared to control sandflies fed blood without IgMn.

“It’s a perfect storm,” said Valenzuela. To reproduce, “You need to have these three elements together. It begins with the inside of the vector, the presence of the parasite, and the parasite using IgMn from the blood meal in the sandfly gut.”

References

  1. Akopyants NS, et al. Science. 2009;324(5924):265-268.
  2. Serafim TD, et al. Nature. 2023;623(7985):149-156.