| Title: |
Macrophages are significant producers of IL-1beta during C. muridarum genital tract infection and IL-1beta secretion is dependent on chlamydial viability but not growth (133.3) |
| Authors: |
Prantner, Daniel; Brade, Helmut; Rank, Roger; Nagarajan, Uma |
| Source: |
The Journal of Immunology ; volume 182, issue Supplement_1, page 133.3-133.3 ; ISSN 1550-6606 0022-1767 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2009 |
| Description: |
Recent findings have implicated secretion of the proinflammatory cytokine interleukin-1β as a crucial player in female genital tract pathology during chlamydial infection. However, the major cellular source of IL-1β during an in vivo infection and mechanistic details of its release have yet to be determined. In the present study, flow cytometry was used to isolate highly enriched cell populations from the genital tracts of C. muridarum infected mice at the peak of IL-1β secretion. Purified F4/80+ macrophages and Ly-6G+ neutrophils, but not CD45- epithelial cells, expressed high levels of both IL-1β mRNA and protein. Macrophages infected with C. muridarum in vitro secrete low amounts of IL-1β, however they can be induced to secrete high amounts when prestimulated with E. coli LPS prior to infection. Prestimulation with purified LPS from C trachomatis L2 was also sufficient to amplify IL-1β secretion, suggesting that prestimulation by chlamydial ligands could account for the high levels of IL-1β observed in vivo. Using LPS prestimulated macrophages as a model system, it was further determined that IL-1β secretion was dependent on activation of the protease caspase-1 in a manner that required both potassium efflux and the activity of serine proteases. Additionally, chlamydial-induced IL-1β secretion was blocked when chlamydiae were inactivated by UV irradiation or heat treatment but occurred normally during treatment with chloramphenicol, rifampin, and INP0007, illustrating that only bacterial viability and not bacterial growth is necessary for this response. This study was supported by NIH grant #AI067678. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.4049/jimmunol.182.supp.133.3 |
| Availability: |
https://doi.org/10.4049/jimmunol.182.supp.133.3; https://academic.oup.com/jimmunol/article/182/Supplement_1/133.3/8015162 |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.B35EC699 |
| Database: |
BASE |