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

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 Microbe

journal_title

Cell host & microbe

authors

Cohen NR,Tatituri RV,Rivera A,Watts GF,Kim EY,Chiba A,Fuchs BB,Mylonakis E,Besra GS,Levitz SM,Brigl M,Brenner MB

doi

10.1016/j.chom.2011.09.011

subject

Has Abstract

pub_date

2011-11-17 00:00:00

pages

437-50

issue

5

eissn

1931-3128

issn

1934-6069

pii

S1931-3128(11)00330-1

journal_volume

10

pub_type

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