Publication Date:
2012-06-16
Description:
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-alpha 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Salmon, Didier -- Vanwalleghem, Gilles -- Morias, Yannick -- Denoeud, Julie -- Krumbholz, Carsten -- Lhomme, Frederic -- Bachmaier, Sabine -- Kador, Markus -- Gossmann, Jasmin -- Dias, Fernando Braga Stehling -- De Muylder, Geraldine -- Uzureau, Pierrick -- Magez, Stefan -- Moser, Muriel -- De Baetselier, Patrick -- Van Den Abbeele, Jan -- Beschin, Alain -- Boshart, Michael -- Pays, Etienne -- New York, N.Y. -- Science. 2012 Jul 27;337(6093):463-6. doi: 10.1126/science.1222753. Epub 2012 Jun 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Parasitology, Institute for Molecular Biology and Medicine, Universite Libre de Bruxelles, 12, rue des Professeurs Jeener et Brachet, B6041 Gosselies, Belgium. salmon@bioqmed.ufrj.br〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22700656" target="_blank"〉PubMed〈/a〉
Keywords:
Adenylyl Cyclases/chemistry/genetics/*metabolism
;
Animals
;
Catalytic Domain
;
Cell Line
;
Cyclic AMP/metabolism
;
Cyclic AMP-Dependent Protein Kinases/metabolism
;
Enzyme Activation
;
Host-Parasite Interactions
;
*Immunity, Innate
;
Liver/cytology
;
Mice
;
Mice, Inbred C57BL
;
Mutagenesis, Site-Directed
;
Myeloid Cells/immunology
;
Parasitemia
;
Phagocytosis
;
Protozoan Proteins/chemistry/genetics/*metabolism
;
Recombinant Fusion Proteins/metabolism
;
Trypanosoma brucei brucei/*enzymology/growth & development/*immunology
;
Trypanosomiasis, African/*immunology/metabolism/parasitology
;
Tumor Necrosis Factor-alpha/biosynthesis/blood
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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