Innate recognition of cell wall β-Glucans drives invariant natural killer T cell responses against fungi

Nadia R. Cohen, Raju V.V. Tatituri, Amariliz Rivera, Gerald F.M. Watts, Edy Y. Kim, Asako Chiba, Beth B. Fuchs, Eleftherios Mylonakis, Gurdyal S. Besra, Stuart M. Levitz, Manfred Brigl, Michael B. Brenner

Research output: Contribution to journalArticlepeer-review

95 Scopus citations


iNKT cells are innate T lymphocytes recognizing endogenous and foreign lipid antigens presented in the MHC-like molecule CD1d. The semi-invariant iNKT cell TCR can detect certain bacterial and parasitic lipids and drive iNKT cell responses. How iNKT cells respond to fungi, however, is unknown. We found that CD1d-deficient mice, which lack iNKT cells, poorly control infection with the fungal pathogen Aspergillus fumigatus. Furthermore, A. fumigatus rapidly activates iNKT cells in vivo and in vitro in the presence of APCs. Surprisingly, despite a requirement for CD1d recognition, the antifungal iNKT cell response does not require fungal lipids. Instead, Dectin-1- and MyD88-mediated responses to β-1,3 glucans, major fungal cell-wall polysaccharides, trigger IL-12 production by APCs that drives self-reactive iNKT cells to secrete IFN-γ. Innate recognition of β-1,3 glucans also drives iNKT cell responses against Candida, Histoplasma, and Alternaria, suggesting that this mechanism may broadly define the basis for antifungal iNKT cell responses.

Original languageEnglish (US)
Pages (from-to)437-450
Number of pages14
JournalCell Host and Microbe
Issue number5
StatePublished - Nov 17 2011

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology


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