کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3416804 | 1225151 | 2010 | 7 صفحه PDF | دانلود رایگان |
The physiological conditions encountered by pathogenic mycobacteria inside their hosts significantly influence their adaptation, virulence, and gene expression. Current in vitro models investigating host-pathogen interactions of Mycobacterium avium subsp. paratuberculosis use 37 °C, the normal body temperatures of mice and humans. However since the physiological temperature of MAP's natural host is 39 °C, we hypothesized that host and pathogen behavior to vary considerably in comparison to 37 °C. Our MAP-macrophage interaction studies show striking differences in regards to velocity of cell invasion of MAP as well as bacterial and host gene regulation at 39 °C compared with 37 °C. Upregulation of host genes (nod2, tlr2, mapkp38 and il-10) follow a similar trend at 37 °C and 39 °C; however, there is over a five-fold increase as early as 0.5 and 2 h in 39 °C treatments. While host signaling is completed by 48 h p.i. at 39 °C in MDMs cultures due to early cell death, signaling and infection is sustained at 37 °C. Surprisingly, transcription of MAP genes did not show a set pattern and were upregulated at different time points for both temperatures. Interestingly, MAP genes encoding a lipase (lipN) and an oxidoreductase (MAP3464) are staggered at 39 °C, while they increase steadily at 37 °C. In conclusion, infection and culture at a physiologically relevant temperature influences host-pathogen interaction, which may have far reaching ramifications including for currently used animal models, in vitro culture methods, bacterial pathogenesis and host responses, and vaccine candidate design and screening.
Journal: Microbial Pathogenesis - Volume 48, Issue 5, May 2010, Pages 143–149