Skip to main content

LAB/NTAL facilitates fungal/PAMP-induced IL-12 and IFN-γ production by repressing β-catenin activation in dendritic cells.

Publication ,  Journal Article
Orr, SJ; Burg, AR; Chan, T; Quigley, L; Jones, GW; Ford, JW; Hodge, D; Razzook, C; Sarhan, J; Jones, YL; Whittaker, GC; Boelte, KC; Lyakh, L ...
Published in: PLoS Pathog
May 2013

Fungal pathogens elicit cytokine responses downstream of immunoreceptor tyrosine-based activation motif (ITAM)-coupled or hemiITAM-containing receptors and TLRs. The Linker for Activation of B cells/Non-T cell Activating Linker (LAB/NTAL) encoded by Lat2, is a known regulator of ITAM-coupled receptors and TLR-associated cytokine responses. Here we demonstrate that LAB is involved in anti-fungal immunity. We show that Lat2-/- mice are more susceptible to C. albicans infection than wild type (WT) mice. Dendritic cells (DCs) express LAB and we show that it is basally phosphorylated by the growth factor M-CSF or following engagement of Dectin-2, but not Dectin-1. Our data revealed a unique mechanism whereby LAB controls basal and fungal/pathogen-associated molecular patterns (PAMP)-induced nuclear β-catenin levels. This in turn is important for controlling fungal/PAMP-induced cytokine production in DCs. C. albicans- and LPS-induced IL-12 and IL-23 production was blunted in Lat2-/- DCs. Accordingly, Lat2-/- DCs directed reduced Th1 polarization in vitro and Lat2-/- mice displayed reduced Natural Killer (NK) and T cell-mediated IFN-γ production in vivo/ex vivo. Thus our data define a novel link between LAB and β-catenin nuclear accumulation in DCs that facilitates IFN-γ responses during anti-fungal immunity. In addition, these findings are likely to be relevant to other infectious diseases that require IL-12 family cytokines and an IFN-γ response for pathogen clearance.

Duke Scholars

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

May 2013

Volume

9

Issue

5

Start / End Page

e1003357

Location

United States

Related Subject Headings

  • beta Catenin
  • Virology
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Lectins, C-Type
  • Interleukin-12
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Orr, S. J., Burg, A. R., Chan, T., Quigley, L., Jones, G. W., Ford, J. W., … McVicar, D. W. (2013). LAB/NTAL facilitates fungal/PAMP-induced IL-12 and IFN-γ production by repressing β-catenin activation in dendritic cells. PLoS Pathog, 9(5), e1003357. https://doi.org/10.1371/journal.ppat.1003357
Orr, Selinda J., Ashley R. Burg, Tim Chan, Laura Quigley, Gareth W. Jones, Jill W. Ford, Deborah Hodge, et al. “LAB/NTAL facilitates fungal/PAMP-induced IL-12 and IFN-γ production by repressing β-catenin activation in dendritic cells.PLoS Pathog 9, no. 5 (May 2013): e1003357. https://doi.org/10.1371/journal.ppat.1003357.
Orr SJ, Burg AR, Chan T, Quigley L, Jones GW, Ford JW, et al. LAB/NTAL facilitates fungal/PAMP-induced IL-12 and IFN-γ production by repressing β-catenin activation in dendritic cells. PLoS Pathog. 2013 May;9(5):e1003357.
Orr, Selinda J., et al. “LAB/NTAL facilitates fungal/PAMP-induced IL-12 and IFN-γ production by repressing β-catenin activation in dendritic cells.PLoS Pathog, vol. 9, no. 5, May 2013, p. e1003357. Pubmed, doi:10.1371/journal.ppat.1003357.
Orr SJ, Burg AR, Chan T, Quigley L, Jones GW, Ford JW, Hodge D, Razzook C, Sarhan J, Jones YL, Whittaker GC, Boelte KC, Lyakh L, Cardone M, O’Connor GM, Tan C, Li H, Anderson SK, Jones SA, Zhang W, Taylor PR, Trinchieri G, McVicar DW. LAB/NTAL facilitates fungal/PAMP-induced IL-12 and IFN-γ production by repressing β-catenin activation in dendritic cells. PLoS Pathog. 2013 May;9(5):e1003357.

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

May 2013

Volume

9

Issue

5

Start / End Page

e1003357

Location

United States

Related Subject Headings

  • beta Catenin
  • Virology
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Lectins, C-Type
  • Interleukin-12