期刊
JOURNAL OF IMMUNOLOGY
卷 181, 期 8, 页码 5560-5567出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.8.5560
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资金
- Trudeau Institute Training Fellowship [T32 AI49823]
- National Institutes of Health [R01-AI67723, R01-A1057588, R01-AI61577, R01-AI26918, U54-AI057158-Lipkin]
- New York Community Trust-Heiser Fund Fellowship and Career Development Award [AI057158]
At the temperature of its flea vector (similar to 20-30 degrees C), the causative agent of plague, Yersinia pestis, expresses a profile of genes distinct from those expressed in a mammalian host (37 degrees C). When dendritic cells (DC) are exposed to Y. pestis grown at 26 degrees C (Y. pestis-26 degrees), they secrete copious amounts of IL-12p40 homodimer (IL-12(p40)(2)). In contrast, when DCs are exposed to Y. pestis grown at 37 degrees C (Y. pestis-37 degrees), they transcribe very little IL-12p40, which is secreted as IL-12p40 monomer (IL-12p40). Y. pestis-26 degrees also induces migration of DCs to the homeostatic chemokine CCL19, whereas Y. pestis-37 degrees does not; migratory DCs are positive for IL-12p40 transcription and secrete mostly IL-12(p40)(2); DCs lacking IL-12p40 do not migrate. Expression of acyltransferase LpxL from Escherichia coli in Y. pestis-37 degrees results in the production of a hexa-acylated lipid A, also seen in Y. pestis-26 degrees, rather than tetra-acylated lipid A normally seen in Y. pestis-37 degrees. The LpxL-expressing Y. pestis-37 degrees promotes DC IL-12(p40)(2) production and induction of DC migration. In addition, absence of TLR4 ablates production of IL-12(p40)(2) in DC exposed to Y. pestis-26 degrees. The data demonstrate the molecular pathway by which Y pestis evades induction of early DC activation as measured by migration and IL-12(p40)(2) production.
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