Cross-species protection suggests Entamoeba histolytica trogocytosis enables complement resistance through the transfer of negative regulators of complement activation.

Entamoeba histolytica is a major cause of diarrheal disease. E. histolytica trophozoites ("amoebae") can invade the intestine and disseminate via the bloodstream, resisting complement lysis through unknown mechanisms. Amoebae kill human cells by performing trogocytosis. After performing trogocytosis, amoebae display human proteins on their own surface and are resistant to lysis by human serum. In this study, we sought to further evaluate the mechanism by which amoebae resist complement lysis. To test if complement is responsible for lysis of amoebae, C3-depleted serum was compared to replete serum, and C3 was indeed required for lysis. Amoebae were allowed to perform trogocytosis of human cells and exposed to mouse serum. Although they had performed trogocytosis on a different species than the source of the serum, they were protected from lysis. To test if the protection from lysis by mouse serum was due to the functional interchangeability of human and mouse complement pathway proteins, human CD46 or CD55 (negative regulators of complement activation) were exogenously expressed. Amoebae that expressed human CD46 or CD55 were protected from lysis by mouse serum, indicating that display of human proteins was sufficient to inhibit mouse complement activation. Finally, amoebae were allowed to perform trogocytosis of a cell type in which the complement pathway is not conserved, and they did not become resistant to lysis. Overall, these findings are consistent with the model that trogocytosis enables amoebic acquisition and display of host proteins, including negative regulators of the complement pathway, that provide protection from complement lysis. Since other microbes can perform trogocytosis, this novel mechanism for complement resistance might apply to other infections.