Effects of LPS-mediated bystander activation in the innate immune system.

Abstract:

:LPS induces dendritic cell (DC) activation, but the precise in vivo mechanism is unclear since DCs express low levels of TLR4. Here, it is shown that DCs can be activated in response to LPS through a bystander mechanism. This result was obtained using chimeric mice reconstituted with LPS-responsive and nonresponsive bone marrow cells. Thus, after indirect in vivo conditioning by LPS, bystander-activated DCs (LPS nonresponsive) up-regulated CD86. This up-regulation occurred even when LPS-responsive cells were MyD88 deficient. Functional analysis demonstrated that in vivo LPS conditioning endowed both the LPS-responsive and bystander cells with the ability to produce IFN-gamma in response to TLR9 stimulation in vitro. IFN-gamma production was also shown to be important for enhanced T-bet gene expression but not important for up-regulation of CD86. To investigate aspects of the mechanism, we used intracellular cytokine staining and found that NKDCs were responsible for at least some of the IFN-gamma production. Thus, our in vivo results demonstrated that bacterial LPS can bridge activation of various cellular populations of the innate immune system through a bystander mechanism.

journal_name

J Leukoc Biol

authors

Yadav R,Zammit DJ,Lefrancois L,Vella AT

doi

10.1189/jlb.0406253

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

1251-61

issue

6

eissn

0741-5400

issn

1938-3673

pii

jlb.0406253

journal_volume

80

pub_type

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