Adenylate cyclases of Trypanosoma brucei inhibit the innate immune response of the host.

TitleAdenylate cyclases of Trypanosoma brucei inhibit the innate immune response of the host.
Publication TypeJournal Article
Year of Publication2012
AuthorsSalmon, D., Vanwalleghem G., Morias Y., Denoeud J., Krumbholz C., Lhommé F., Bachmaier S., Kador M., Gossmann J., Dias F. Braga Steh, De Muylder G., Uzureau P., Magez S., Moser M., De Baetselier P., Van Den Abbeele J., Beschin A., Boshart M., and Pays E.
JournalScience
Volume337
Issue6093
Pagination463-6
Date Published2012 Jul 27
ISSN1095-9203
KeywordsAdenylate Cyclase, Animals, Catalytic Domain, Cell Line, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Enzyme Activation, Host-Parasite Interactions, Immunity, Innate, Liver, Mice, Mice, Inbred C57BL, Mutagenesis, Site-Directed, Myeloid Cells, Parasitemia, Phagocytosis, Protozoan Proteins, Recombinant Fusion Proteins, Trypanosoma brucei brucei, Trypanosomiasis, African, Tumor Necrosis Factor-alpha
Abstract

The parasite Trypanosoma brucei possesses a large family of transmembrane receptor-like adenylate cyclases. Activation of these enzymes requires the dimerization of the catalytic domain and typically occurs under stress. Using a dominant-negative strategy, we found that reducing adenylate cyclase activity by about 50% allowed trypanosome growth but reduced the parasite's ability to control the early innate immune defense of the host. Specifically, activation of trypanosome adenylate cyclase resulting from parasite phagocytosis by liver myeloid cells inhibited the synthesis of the trypanosome-controlling cytokine tumor necrosis factor-α through activation of protein kinase A in these cells. Thus, adenylate cyclase activity of lyzed trypanosomes favors early host colonization by live parasites. The role of adenylate cyclases at the host-parasite interface could explain the expansion and polymorphism of this gene family.

DOI10.1126/science.1222753
Alternate JournalScience
PubMed ID22700656
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