Cyanovirin-N inhibits mannose-dependent Mycobacterium-C-type lectin interactions but does not protect against murine tuberculosis

J Immunol. 2012 Oct 1;189(7):3585-92. doi: 10.4049/jimmunol.1102408. Epub 2012 Aug 31.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / administration & dosage
  • Bacterial Proteins / physiology*
  • Carrier Proteins / administration & dosage
  • Carrier Proteins / physiology*
  • Cell Line
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / microbiology
  • Disease Models, Animal
  • Humans
  • Lectins, C-Type / antagonists & inhibitors*
  • Lectins, C-Type / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Mannose / metabolism*
  • Mannose / physiology
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / immunology
  • Monocytes / metabolism
  • Monocytes / microbiology
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / metabolism*
  • Protein Binding / drug effects
  • Protein Binding / immunology
  • Treatment Outcome
  • Tuberculosis / immunology*
  • Tuberculosis / microbiology
  • Tuberculosis / prevention & control

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Lectins, C-Type
  • cyanovirin N
  • Mannose