Histoplasma capsulatum α-(1,3)-glucan blocks innate immune recognition by the β-glucan receptor

Chad A. Rappleye, Linda Groppe Eissenberg, William E. Goldman

Research output: Contribution to journalArticlepeer-review

335 Scopus citations


Successful infection by fungal pathogens depends on subversion of host immune mechanisms that detect conserved cell wall components such as β-glucans. A less common polysaccharide, α-(1,3)-glucan, is a cell wall constituent of most fungal respiratory pathogens and has been correlated with pathogenicity or linked directly to virulence. However, the precise mechanism by which α-(1,3)-glucan promotes fungal virulence is unknown. Here, we show that α-(1,3)-glucan is present in the outermost layer of the Histoplasma capsulation yeast cell wall and contributes to pathogenesis by concealing immunostimulatory β-glucans from detection by host phagocytic cells. Production of proinflammatory TNFα by phagocytes was suppressed either by the presence of the α-(1,3)-glucan layer on yeast cells or by RNA interference based depletion of the host β-glucan receptor dectin-1. Thus, we have functionally defined key molecular components influencing the initial host-pathogen interaction in histoplasmosis and have revealed an important mechanism by which H. capsulatum thwarts the host immune system. Furthermore, we propose that the degree of this evasion contributes to the difference in pathogenic potential between dimorphic fungal pathogens and opportunistic fungi.

Original languageEnglish
Pages (from-to)1366-1370
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number4
StatePublished - Jan 23 2007


  • Cell wall
  • Dectin-1
  • Fungal pathogenesis
  • Macrophage
  • Virulence factor


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