Phagosomal degradation increases TLR access to bacterial ligands and enhances macrophage sensitivity to bacteria.
Phagosomal degradation increases TLR access to bacterial ligands and enhances macrophage sensitivity to bacteria.
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DOI：
10.4049/jimmunol.1100232
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发表时间：
2011-12-01
期刊：
影响因子：
--
通讯作者：
Underhill DM
中科院分区：
文献类型：
--
作者：
Wolf AJ;Arruda A;Reyes CN;Kaplan AT;Shimada T;Shimada K;Arditi M;Liu G;Underhill DM
Signaling by innate immune receptors initiates and orchestrates the overall immune responses to infection. Macrophage receptors recognizing pathogens can be broadly grouped into surface receptors and receptors restricted to intracellular compartments, such as phagosomes and the cytoplasm. There is an expectation that ingestion and degradation of microorganisms by phagocytes contributes to activation of intracellular innate receptors, although direct demonstrations of this are rare and many model ligands are studied in soluble form, outside of their microbial context. By comparing a wild-type strain of Staphylococcus aureus and a lysozyme-sensitive mutant, we have been able to directly address the role of degradation of live bacteria by mouse macrophages in determining the overall innate cellular inflammatory response. Our investigations revealed a biphasic response to S. aureus that consisted of an initial signal resulting from the engagement of surface TLR2, followed by a later, second wave on inflammatory gene induction. This second wave of inflammatory signaling was dependent on and correlated with the timing of bacterial degradation in phagosomes. We found that TLR2 signaling followed by TLR2/TLR9 signaling enhanced sensitivity to small numbers of bacteria. We further found that treating wild-type bacteria with the peptidoglycan synthesis-inhibiting antibiotic vancomycin made S. aureus more susceptible to degradation and resulted in increased inflammatory responses, similar to those observed for mutant degradation-sensitive bacteria.
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作者：
Shaw, Michael H.;Reimer, Thornik;Kim, Yun-Gi;Nunez, Gabriel
通讯作者：
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影响因子：
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DOI：
10.4049/jimmunol.0802197
发表时间：
2009-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
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通讯作者：
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DOI：
10.4049/jimmunol.1000110
发表时间：
2010-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Ip WK;Sokolovska A;Charriere GM;Boyer L;Dejardin S;Cappillino MP;Yantosca LM;Takahashi K;Moore KJ;Lacy-Hulbert A;Stuart LM
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