title: Cyanovirin-N inhibits mannose-dependent Mycobacterium-C-type lectin interactions but does not protect against murine tuberculosis.
abstract: Cyanovirin-N (CV-N) is a mannose-binding lectin that inhibits HIV-1 infection by blocking mannose-dependent target cell entry via C-type lectins. Like HIV-1, Mycobacterium tuberculosis expresses mannosylated surface structures and exploits C-type lectins to gain cell access. In this study, we investigated whether CV-N, like HIV-1, can inhibit M. tuberculosis infection. We found that CV-N specifically interacted with mycobacteria by binding to the mannose-capped lipoglycan lipoarabinomannan. Furthermore, CV-N competed with the C-type lectins DC-SIGN and mannose receptor for ligand binding and inhibited the binding of M. tuberculosis to dendritic cells but, unexpectedly, not to macrophages. Subsequent in vivo infection experiments in a mouse model demonstrated that, despite its activity, CV-N did not inhibit or delay M. tuberculosis infection. This outcome argues against a critical role for mannose-dependent C-type lectin interactions during the initial stages of murine M. tuberculosis infection and suggests that, depending on the circumstances, M. tuberculosis can productively infect cells using different modes of entry.
authors.affiliation: Department of Medical Microbiology and Infection Control, Free University Medical Center, 1081 BT Amsterdam, The Netherlands.
authors.forename: Nicole N
authors.initials: NN
authors.lastname: Driessen
authors.forename: Helena I M
authors.initials: HI
authors.lastname: Boshoff
authors.forename: Janneke J
authors.initials: JJ
authors.lastname: Maaskant
authors.forename: Sebastiaan A C
authors.initials: SA
authors.lastname: Gilissen
authors.forename: Simone
authors.initials: S
authors.lastname: Vink
authors.forename: Astrid M
authors.initials: AM
authors.lastname: van der Sar
authors.forename: Christina M J E
authors.initials: CM
authors.lastname: Vandenbroucke-Grauls
authors.forename: Carole A
authors.initials: CA
authors.lastname: Bewley
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Appelmelk
authors.forename: Jeroen
authors.initials: J
authors.lastname: Geurtsen
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000502:physiology*; D002352:Carrier Proteins / Q000008:administration & dosage / Q000502:physiology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D004195:Disease Models, Animal; D006801:Humans; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008358:Mannose / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D037181:Lectins, C-Type; C107733:cyanovirin N; D008358:Mannose