Role of Toll-like receptor signaling in the apoptotic response of macrophages to Yersinia infection.

Abstract:

:Macrophages encode several Toll-like receptors (TLRs) that recognize bacterial components, such as lipoproteins (TLR2) or lipopolysaccharides (TLR4), and activate multiple signaling pathways. Activation of transcription factor NF-kappaB by TLR2 or TLR4 signaling promotes proinflammatory and cell survival responses. Alternatively, TLR2 or TLR4 signaling can promote apoptosis if the activation of NF-kappaB is blocked. The gram-negative bacterial pathogen Yersinia pseudotuberculosis secretes into macrophages a protease (YopJ) that inhibits the activation of NF-kappaB and promotes apoptosis. We show that primary macrophages expressing constitutively active inhibitor kappaB kinase beta (IKKbeta) are completely resistant to YopJ-dependent apoptosis, indicating that YopJ inhibits signaling upstream of IKKbeta. Apoptosis is reduced two- to threefold in TLR4(-/-) macrophages infected with Y. pseudotuberculosis, while the apoptotic response of TLR2(-/-) macrophages to Y. pseudotuberculosis infection is equivalent to that of wild-type macrophages. Therefore, TLR4 is the primary source of apoptotic signaling in Yersinia-infected macrophages. Our results also show that a small percentage of macrophages can die as a result of an apoptotic process that is YopJ dependent but does not require TLR2 or TLR4 signaling.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Zhang Y,Bliska JB

doi

10.1128/iai.71.3.1513-1519.2003

keywords:

subject

Has Abstract

pub_date

2003-03-01 00:00:00

pages

1513-9

issue

3

eissn

0019-9567

issn

1098-5522

journal_volume

71

pub_type

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