Activation of human monocyte-derived dendritic cells by Burkholderia pseudomallei does not require binding to the C-type lectin DC-SIGN

Jaruek Charoensap, Anneke Engering, Pongsak Utaisincharoen, Yvette van Kooyk, Stitaya Sirisinha

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Dendritic cells (DCs) are essential in regulating adaptive immunity. DC-SIGN (DC-specific ICAM-grabbing nonintegrin) is a C-type lectin receptor that is expressed mainly by DCs. Accumulating evidence supports that certain pathogens target DC-SIGN to escape host immunity. To investigate a possible role of DC-SIGN in Burkholderia pseudomallei infection, we initially screened its DC-SIGN binding activity by an ELISA method utilizing a DC-SIGN-Fc chimeric protein and found that all of the B. pseudomallei strains tested failed to bind DC-SIGN. However, one strain, the LPS mutant SRM117, which lacks the type II O-polysaccharide expression, actually bound DC-SIGN, in contrast to its wild-type counterpart 1026b (P<0.001). We also found that, although the LPS mutant could readily activate monocyte-derived human DCs, it induced lower levels of IL-12p70 and IL-10 production than its wild-type counterpart (P<0.01). By contrast, the wild-type and the LPS mutants were indistinguishable from one another in terms of T(H)1/T(H)2 differentiation. Altogether, these data suggest that, unlike other certain host pathogen interactions, activation of DCs by B. pseudomallei is not dependent on DC-SIGN. We also found evidence that the LPS mutant that binds DC-SIGN has a suppressive effect on DC cytokine production.

Original languageEnglish
Pages (from-to)S76-81
JournalTransactions of the Royal Society of Tropical Medicine and Hygiene
Volume102 Suppl 1
DOIs
Publication statusPublished - Dec 2008

Cite this

@article{868cb76d8b9442968f9a2c86cf3d8826,
title = "Activation of human monocyte-derived dendritic cells by Burkholderia pseudomallei does not require binding to the C-type lectin DC-SIGN",
abstract = "Dendritic cells (DCs) are essential in regulating adaptive immunity. DC-SIGN (DC-specific ICAM-grabbing nonintegrin) is a C-type lectin receptor that is expressed mainly by DCs. Accumulating evidence supports that certain pathogens target DC-SIGN to escape host immunity. To investigate a possible role of DC-SIGN in Burkholderia pseudomallei infection, we initially screened its DC-SIGN binding activity by an ELISA method utilizing a DC-SIGN-Fc chimeric protein and found that all of the B. pseudomallei strains tested failed to bind DC-SIGN. However, one strain, the LPS mutant SRM117, which lacks the type II O-polysaccharide expression, actually bound DC-SIGN, in contrast to its wild-type counterpart 1026b (P<0.001). We also found that, although the LPS mutant could readily activate monocyte-derived human DCs, it induced lower levels of IL-12p70 and IL-10 production than its wild-type counterpart (P<0.01). By contrast, the wild-type and the LPS mutants were indistinguishable from one another in terms of T(H)1/T(H)2 differentiation. Altogether, these data suggest that, unlike other certain host pathogen interactions, activation of DCs by B. pseudomallei is not dependent on DC-SIGN. We also found evidence that the LPS mutant that binds DC-SIGN has a suppressive effect on DC cytokine production.",
keywords = "Burkholderia pseudomallei/genetics, Cell Adhesion Molecules/immunology, Cell Line, Dendritic Cells/immunology, Humans, Immunity, Cellular, Lectins, C-Type/immunology, Melioidosis/immunology, Receptors, Cell Surface/immunology",
author = "Jaruek Charoensap and Anneke Engering and Pongsak Utaisincharoen and {van Kooyk}, Yvette and Stitaya Sirisinha",
year = "2008",
month = "12",
doi = "10.1016/S0035-9203(08)70020-8",
language = "English",
volume = "102 Suppl 1",
pages = "S76--81",
journal = "Transactions of the Royal Society of Tropical Medicine and Hygiene",
issn = "0035-9203",
publisher = "Oxford University Press",

}

Activation of human monocyte-derived dendritic cells by Burkholderia pseudomallei does not require binding to the C-type lectin DC-SIGN. / Charoensap, Jaruek; Engering, Anneke; Utaisincharoen, Pongsak; van Kooyk, Yvette; Sirisinha, Stitaya.

In: Transactions of the Royal Society of Tropical Medicine and Hygiene, Vol. 102 Suppl 1, 12.2008, p. S76-81.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Activation of human monocyte-derived dendritic cells by Burkholderia pseudomallei does not require binding to the C-type lectin DC-SIGN

AU - Charoensap, Jaruek

AU - Engering, Anneke

AU - Utaisincharoen, Pongsak

AU - van Kooyk, Yvette

AU - Sirisinha, Stitaya

PY - 2008/12

Y1 - 2008/12

N2 - Dendritic cells (DCs) are essential in regulating adaptive immunity. DC-SIGN (DC-specific ICAM-grabbing nonintegrin) is a C-type lectin receptor that is expressed mainly by DCs. Accumulating evidence supports that certain pathogens target DC-SIGN to escape host immunity. To investigate a possible role of DC-SIGN in Burkholderia pseudomallei infection, we initially screened its DC-SIGN binding activity by an ELISA method utilizing a DC-SIGN-Fc chimeric protein and found that all of the B. pseudomallei strains tested failed to bind DC-SIGN. However, one strain, the LPS mutant SRM117, which lacks the type II O-polysaccharide expression, actually bound DC-SIGN, in contrast to its wild-type counterpart 1026b (P<0.001). We also found that, although the LPS mutant could readily activate monocyte-derived human DCs, it induced lower levels of IL-12p70 and IL-10 production than its wild-type counterpart (P<0.01). By contrast, the wild-type and the LPS mutants were indistinguishable from one another in terms of T(H)1/T(H)2 differentiation. Altogether, these data suggest that, unlike other certain host pathogen interactions, activation of DCs by B. pseudomallei is not dependent on DC-SIGN. We also found evidence that the LPS mutant that binds DC-SIGN has a suppressive effect on DC cytokine production.

AB - Dendritic cells (DCs) are essential in regulating adaptive immunity. DC-SIGN (DC-specific ICAM-grabbing nonintegrin) is a C-type lectin receptor that is expressed mainly by DCs. Accumulating evidence supports that certain pathogens target DC-SIGN to escape host immunity. To investigate a possible role of DC-SIGN in Burkholderia pseudomallei infection, we initially screened its DC-SIGN binding activity by an ELISA method utilizing a DC-SIGN-Fc chimeric protein and found that all of the B. pseudomallei strains tested failed to bind DC-SIGN. However, one strain, the LPS mutant SRM117, which lacks the type II O-polysaccharide expression, actually bound DC-SIGN, in contrast to its wild-type counterpart 1026b (P<0.001). We also found that, although the LPS mutant could readily activate monocyte-derived human DCs, it induced lower levels of IL-12p70 and IL-10 production than its wild-type counterpart (P<0.01). By contrast, the wild-type and the LPS mutants were indistinguishable from one another in terms of T(H)1/T(H)2 differentiation. Altogether, these data suggest that, unlike other certain host pathogen interactions, activation of DCs by B. pseudomallei is not dependent on DC-SIGN. We also found evidence that the LPS mutant that binds DC-SIGN has a suppressive effect on DC cytokine production.

KW - Burkholderia pseudomallei/genetics

KW - Cell Adhesion Molecules/immunology

KW - Cell Line

KW - Dendritic Cells/immunology

KW - Humans

KW - Immunity, Cellular

KW - Lectins, C-Type/immunology

KW - Melioidosis/immunology

KW - Receptors, Cell Surface/immunology

U2 - 10.1016/S0035-9203(08)70020-8

DO - 10.1016/S0035-9203(08)70020-8

M3 - Article

VL - 102 Suppl 1

SP - S76-81

JO - Transactions of the Royal Society of Tropical Medicine and Hygiene

JF - Transactions of the Royal Society of Tropical Medicine and Hygiene

SN - 0035-9203

ER -