| Autor: |
Uittenbogaard, Annette M., Chelvarajan, R. Lakshman, Myers-Morales, Tanya, Gorman, Amanda A., Brickey, W. June, Ye, Zhan, Kaplan, Alan M., Cohen, Donald A., Ting, Jenny P.-Y., Straley, Susan C. |
| Předmět: |
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| Zdroj: |
Frontiers in Cellular & Infection Microbiology; Nov2012, Vol. 2, preceding p1-38, 39p |
| Abstrakt: |
YopM is one of the six "effector Yops" of the human-pathogenic Yersinia, but its mechanism has 45 not been defined. After delivery to J774A.1 monocyte-like cells, YopM can rapidly bind and 46 activate the serine/threonine kinases RSK1 and PRK2. However, in infected mice, effects of Y. pestis YopM have been seen only after 24 to 48 h post infection (p.i.). To identify potential direct effects of YopM in vivo we tested for effects of YopM at 1h and 16-18h p.i. in mice infected systemically with 106 bacteria. At 16 h p.i., there was a robust host response to both parent and ΔyopM-1 Y. pestis KIM5. Compared to cells from non-infected mice, CD11b+ cells from spleens of infected mice produced more than 100-fold greater IFNγ. In the corresponding sera there were more than 100-fold greater amounts of IFNγ, G-CSF, and CXCL9, as well as more than 10-fold greater amounts of IL-6, CXCL10, and CXCL1. The only YopM-related differences were slightly lower CXCL10 and IL-6 in sera from mice infected 16 h with parent compared to ΔyopM-1 Y. pestis. Microarray analysis of the CD11b+ cells did not identify consistent transcriptional differences of ⩾ 4 fold at 18 h p.i. However, at 1 h p.i. mRNA for early growth response transcription factor 1 (Egr1) was decreased when YopM was present. Bone marrow-derived macrophages infected for 1 h also expressed lower Egr1 message when YopM was present. Infected J774A.1 cells showed greater expression of Egr1 at 1 h p.i. when YopM was present, but this pattern reversed at 3 h. At 6 h p.i., Cxcl10 mRNA was lower in parent strain infected cells. We conclude that decreased Egr1 expression is a very early transcriptional effect of YopM and speculate that a pathway may exist from RSK1 through Egr1. These studies revealed novel early transcriptional effects of YopM but point to a time after 18 h of infection when critical transitional events lead to later major effects on cytokine gene transcription. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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