Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a)

M del Pilar Jiménez-A, S Viriyakosol, L Walls, S K Datta, T Kirkland, S E M Heinsbroek, Gordon Douglas Brown, J Fierer

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Coccidioides posadasii spherules stimulate macrophages to make cytokines via TLR-2 and Dectin-1. We used formalin-killed spherules and 1,3-beta-glucan purified from spherules to stimulate elicited peritoneal macrophages and myeloid dendritic cells (mDCs) from susceptible (C57BL/6) and resistant (DBA/2) mouse strains. DBA/2 macrophages produced more TNF-alpha and IL-6 than macrophages from C57BL/6 mice, and the amount of TNF-alpha made was dependent on both TLR2 and Dectin-1. DCs from C57BL/6 mice made more IL-10 and less IL-23p19 and IL-12p70 than did DBA/2 DC. These responses were inhibited by a monoclonal antibody to Dectin-1. DBA/2 mice expressed full-length Dectin-1, whereas C57BL/6 mice spliced out exon 3, which encodes most of the stalk. RAW cells transduced to express the full-length Dectin-1 responded better to FKS than cells expressing truncated Dectin-1. We compared the isoform of Dectin-1 expressed by 34 C57BL/6 X DBA/2 recombinant inbred (BXD RI) lines with their susceptibility to Coccidioides immitis. In 25 of 34 RI lines susceptibility or resistance corresponded to short or full-length isoforms, respectively. These results suggest that alternative splicing of the Dectin-1 gene contributes to susceptibility of C57BL/6 mice to coccidioidomycosis, and affects the cytokine responses of macrophages and mDCs to spherules.
Original languageEnglish
Pages (from-to)338-348
Number of pages11
JournalGenes and Immunity
Volume9
Issue number4
Early online date17 Apr 2008
DOIs
Publication statusPublished - Jun 2008

Fingerprint

Coccidioides
Inbred C57BL Mouse
Macrophages
Inbred DBA Mouse
Myeloid Cells
Dendritic Cells
Interleukin-23 Subunit p19
Protein Isoforms
Tumor Necrosis Factor-alpha
Cytokines
Coccidioidomycosis
dectin 1
Alternative Splicing
Peritoneal Macrophages
Interleukin-10
Formaldehyde
Exons
Interleukin-6
Monoclonal Antibodies

Keywords

  • alternative splicing
  • animals
  • cell line
  • coccidioides
  • coccidioidomycosis
  • dendritic cells
  • gene expression
  • genetic predisposition to disease
  • immunity, innate
  • interleukin-10
  • macrophages, peritoneal
  • membrane proteins
  • mice
  • mice, inbred C57BL
  • mice, inbred DBA
  • nerve tissue proteins
  • protein isoforms
  • species specificity
  • tumor necrosis factor-alpha

Cite this

del Pilar Jiménez-A, M., Viriyakosol, S., Walls, L., Datta, S. K., Kirkland, T., Heinsbroek, S. E. M., ... Fierer, J. (2008). Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a). Genes and Immunity, 9(4), 338-348. https://doi.org/10.1038/gene.2008.23

Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a). / del Pilar Jiménez-A, M; Viriyakosol, S; Walls, L; Datta, S K; Kirkland, T; Heinsbroek, S E M; Brown, Gordon Douglas; Fierer, J.

In: Genes and Immunity, Vol. 9, No. 4, 06.2008, p. 338-348.

Research output: Contribution to journalArticle

del Pilar Jiménez-A, M, Viriyakosol, S, Walls, L, Datta, SK, Kirkland, T, Heinsbroek, SEM, Brown, GD & Fierer, J 2008, 'Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a)', Genes and Immunity, vol. 9, no. 4, pp. 338-348. https://doi.org/10.1038/gene.2008.23
del Pilar Jiménez-A, M ; Viriyakosol, S ; Walls, L ; Datta, S K ; Kirkland, T ; Heinsbroek, S E M ; Brown, Gordon Douglas ; Fierer, J. / Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a). In: Genes and Immunity. 2008 ; Vol. 9, No. 4. pp. 338-348.
@article{f5330de1ab9740cdb823f3046dd5346a,
title = "Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a)",
abstract = "Coccidioides posadasii spherules stimulate macrophages to make cytokines via TLR-2 and Dectin-1. We used formalin-killed spherules and 1,3-beta-glucan purified from spherules to stimulate elicited peritoneal macrophages and myeloid dendritic cells (mDCs) from susceptible (C57BL/6) and resistant (DBA/2) mouse strains. DBA/2 macrophages produced more TNF-alpha and IL-6 than macrophages from C57BL/6 mice, and the amount of TNF-alpha made was dependent on both TLR2 and Dectin-1. DCs from C57BL/6 mice made more IL-10 and less IL-23p19 and IL-12p70 than did DBA/2 DC. These responses were inhibited by a monoclonal antibody to Dectin-1. DBA/2 mice expressed full-length Dectin-1, whereas C57BL/6 mice spliced out exon 3, which encodes most of the stalk. RAW cells transduced to express the full-length Dectin-1 responded better to FKS than cells expressing truncated Dectin-1. We compared the isoform of Dectin-1 expressed by 34 C57BL/6 X DBA/2 recombinant inbred (BXD RI) lines with their susceptibility to Coccidioides immitis. In 25 of 34 RI lines susceptibility or resistance corresponded to short or full-length isoforms, respectively. These results suggest that alternative splicing of the Dectin-1 gene contributes to susceptibility of C57BL/6 mice to coccidioidomycosis, and affects the cytokine responses of macrophages and mDCs to spherules.",
keywords = "alternative splicing, animals, cell line, coccidioides, coccidioidomycosis, dendritic cells, gene expression, genetic predisposition to disease, immunity, innate, interleukin-10, macrophages, peritoneal, membrane proteins, mice , mice, inbred C57BL, mice, inbred DBA, nerve tissue proteins, protein isoforms, species specificity, tumor necrosis factor-alpha",
author = "{del Pilar Jim{\'e}nez-A}, M and S Viriyakosol and L Walls and Datta, {S K} and T Kirkland and Heinsbroek, {S E M} and Brown, {Gordon Douglas} and J Fierer",
year = "2008",
month = "6",
doi = "10.1038/gene.2008.23",
language = "English",
volume = "9",
pages = "338--348",
journal = "Genes and Immunity",
issn = "1466-4879",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a)

AU - del Pilar Jiménez-A, M

AU - Viriyakosol, S

AU - Walls, L

AU - Datta, S K

AU - Kirkland, T

AU - Heinsbroek, S E M

AU - Brown, Gordon Douglas

AU - Fierer, J

PY - 2008/6

Y1 - 2008/6

N2 - Coccidioides posadasii spherules stimulate macrophages to make cytokines via TLR-2 and Dectin-1. We used formalin-killed spherules and 1,3-beta-glucan purified from spherules to stimulate elicited peritoneal macrophages and myeloid dendritic cells (mDCs) from susceptible (C57BL/6) and resistant (DBA/2) mouse strains. DBA/2 macrophages produced more TNF-alpha and IL-6 than macrophages from C57BL/6 mice, and the amount of TNF-alpha made was dependent on both TLR2 and Dectin-1. DCs from C57BL/6 mice made more IL-10 and less IL-23p19 and IL-12p70 than did DBA/2 DC. These responses were inhibited by a monoclonal antibody to Dectin-1. DBA/2 mice expressed full-length Dectin-1, whereas C57BL/6 mice spliced out exon 3, which encodes most of the stalk. RAW cells transduced to express the full-length Dectin-1 responded better to FKS than cells expressing truncated Dectin-1. We compared the isoform of Dectin-1 expressed by 34 C57BL/6 X DBA/2 recombinant inbred (BXD RI) lines with their susceptibility to Coccidioides immitis. In 25 of 34 RI lines susceptibility or resistance corresponded to short or full-length isoforms, respectively. These results suggest that alternative splicing of the Dectin-1 gene contributes to susceptibility of C57BL/6 mice to coccidioidomycosis, and affects the cytokine responses of macrophages and mDCs to spherules.

AB - Coccidioides posadasii spherules stimulate macrophages to make cytokines via TLR-2 and Dectin-1. We used formalin-killed spherules and 1,3-beta-glucan purified from spherules to stimulate elicited peritoneal macrophages and myeloid dendritic cells (mDCs) from susceptible (C57BL/6) and resistant (DBA/2) mouse strains. DBA/2 macrophages produced more TNF-alpha and IL-6 than macrophages from C57BL/6 mice, and the amount of TNF-alpha made was dependent on both TLR2 and Dectin-1. DCs from C57BL/6 mice made more IL-10 and less IL-23p19 and IL-12p70 than did DBA/2 DC. These responses were inhibited by a monoclonal antibody to Dectin-1. DBA/2 mice expressed full-length Dectin-1, whereas C57BL/6 mice spliced out exon 3, which encodes most of the stalk. RAW cells transduced to express the full-length Dectin-1 responded better to FKS than cells expressing truncated Dectin-1. We compared the isoform of Dectin-1 expressed by 34 C57BL/6 X DBA/2 recombinant inbred (BXD RI) lines with their susceptibility to Coccidioides immitis. In 25 of 34 RI lines susceptibility or resistance corresponded to short or full-length isoforms, respectively. These results suggest that alternative splicing of the Dectin-1 gene contributes to susceptibility of C57BL/6 mice to coccidioidomycosis, and affects the cytokine responses of macrophages and mDCs to spherules.

KW - alternative splicing

KW - animals

KW - cell line

KW - coccidioides

KW - coccidioidomycosis

KW - dendritic cells

KW - gene expression

KW - genetic predisposition to disease

KW - immunity, innate

KW - interleukin-10

KW - macrophages, peritoneal

KW - membrane proteins

KW - mice

KW - mice, inbred C57BL

KW - mice, inbred DBA

KW - nerve tissue proteins

KW - protein isoforms

KW - species specificity

KW - tumor necrosis factor-alpha

U2 - 10.1038/gene.2008.23

DO - 10.1038/gene.2008.23

M3 - Article

C2 - 18418396

VL - 9

SP - 338

EP - 348

JO - Genes and Immunity

JF - Genes and Immunity

SN - 1466-4879

IS - 4

ER -