Complement Camouflage

After nibbling on human cells, amoebae (green) show human proteins (red with blue nuclei) on their surface.

Hannah Miller

Amoebae represent a vast range of single-celled organisms that share an ability to change their shape, extending blobby pseudopods to move around and engulf other cells for food. Several years ago, researchers discovered that the parasitic, diarrhea-causing amoeba Entamoeba histolytica sometimes just nibbled host cells, rather than swallowing them whole. Now, a member of that research team has found that such nibbling, known as trogocytosis, also allows an amoeba to hide from its host’s immune system.

The new study, conducted by Katherine Ralston and colleagues at the University of California, Davis, tracked the interactions between E. histolytica and cells from its human hosts. When E. histolytica were mixed with human cells, amoebae that had engaged in trogocytosis displayed the human cells’ proteins on their own membranes. In contrast, amoebae that had swallowed human cells whole did not show human proteins on their membranes, suggesting that trogocytosis was specifically needed for protein display.

In human cells, such proteins prevent them from being targeted by immune system proteins, known as complement. The researchers hypothesized that displaying the stolen human proteins on their external membranes camouflaged the amoebae, allowing them to avoid being attacked by complement. This was experimentally confirmed. Complement completely wiped out those amoebae that did not engage in trogocytosis. Post-trogocytosis, complement-disguised amoebae remained unhurt, free to roam the body, unhindered.

“Growing awareness of this ‘complement camouflage’ helps us to understand how a pathogen can survive in our bodies, despite how powerful the complement system is in protecting us from infection,” said Ralston. As E. histolytica, the causative agent of amebiasis, infects tens of millions and kills tens of thousands of people annually, understanding how to expose the amoebae to the immune system could save many lives.

Still, many details remain to be worked out, including which proteins are stolen in the process and how the amoebae go about exhibiting them to patrolling immune system components. “We are a long way from counteracting this process therapeutically,” Ralston added, “but understanding the microbe and the pathogenesis of the disease is the first step towards better therapies.” (mBio)