Activation of human monocyte-derived dendritic cells by Burkholderia pseudomallei does not require binding to the C-type lectin DC-SIGN.
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.
Charoensap
Jaruek
J
Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand. cjaruek@yahoo.com
Engering
Anneke
A
Utaisincharoen
Pongsak
P
van Kooyk
Yvette
Y
Sirisinha
Stitaya
S
D016957:Burkholderia pseudomallei / Q000235:genetics / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism*; D008554:Melioidosis / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin