Abstract:
: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.
journal_name
Cell Host Microbejournal_title
Cell host & microbeauthors
Cohen NR,Tatituri RV,Rivera A,Watts GF,Kim EY,Chiba A,Fuchs BB,Mylonakis E,Besra GS,Levitz SM,Brigl M,Brenner MBdoi
10.1016/j.chom.2011.09.011subject
Has Abstractpub_date
2011-11-17 00:00:00pages
437-50issue
5eissn
1931-3128issn
1934-6069pii
S1931-3128(11)00330-1journal_volume
10pub_type
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