Recruitment of human C1 esterase inhibitor controls complement activation on blood stage plasmodium falciparum merozoites

Alexander T. Kennedy, Lakshmi C. Wijeyewickrema, Alisee Huglo, Clara Lin, Robert Pike, Alan Frederick Cowman, Wai-Hong Tham

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17 Citations (Scopus)


The complement system is a front-line defense system that opsonizes and lyses invading pathogens. To survive, microbes exposed to serum must evade the complement response. To achieve this, many pathogens recruit soluble human complement regulators to their surfaces and hijack their regulatory function for protection from complement activation. C1 esterase inhibitor (C1-INH) is a soluble regulator of complement activation that negatively regulates the classical and lectin pathways of complement to protect human tissue from aberrant activation. In this article, we show that Plasmodium falciparum merozoites, the invasive form of blood stage malaria parasites, actively recruit C1-INH to their surfaces when exposed to human serum. We identified PfMSP3.1, a member of the merozoite surface protein 3 family of merozoite surface proteins, as the direct interaction partner. When bound to the merozoite surface, C1-INH retains its ability to complex with and inhibit C1s, MASP1, and MASP2, the activating proteases of the complement cascade. P. falciparum merozoites that lack PfMSP3.1 showed a marked reduction in C1-INH recruitment and increased C3b deposition on their surfaces. However, these δPfMSP3.1 merozoites exhibit enhanced invasion of RBCs in the presence of active complement. This study characterizes an immune-evasion strategy used by malaria parasites and highlights the complex relationship between merozoites and the complement system.

Original languageEnglish
Pages (from-to)4728-4737
Number of pages10
JournalJournal of Immunology
Issue number12
Publication statusPublished - 15 Jun 2017
Externally publishedYes

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