| Title: |
Critical Role for Interleukin-1β (IL-1β) during Chlamydia muridarum Genital Infection and Bacterial Replication-Independent Secretion of IL-1β in Mouse Macrophages |
| Authors: |
Prantner, Daniel; Darville, Toni; Sikes, James D.; Andrews, Charles W.; Brade, Helmut; Rank, Roger G.; Nagarajan, Uma M. |
| Source: |
Infection and Immunity ; volume 77, issue 12, page 5334-5346 ; ISSN 0019-9567 1098-5522 |
| Publisher Information: |
American Society for Microbiology |
| Publication Year: |
2009 |
| Description: |
Recent findings have implicated interleukin-1β (IL-1β) as an important mediator of the inflammatory response in the female genital tract during chlamydial infection. But how IL-1β is produced and its specific role in infection and pathology are unclear. Therefore, our goal was to determine the functional consequences and cellular sources of IL-1β expression during a chlamydial genital infection. In the present study, IL-1β −/− mice exhibited delayed chlamydial clearance and decreased frequency of hydrosalpinx compared to wild-type (WT) mice, implying an important role for IL-1β both in the clearance of infection and in the mediation of oviduct pathology. At the peak of IL-1β secretion in WT mice, the major producers of IL-1β in vivo are F4/80 + macrophages and GR-1 + neutrophils, but not CD45 − epithelial cells. Although elicited mouse macrophages infected with C hlamydia muridarum in vitro secrete minimal IL-1β, in vitro prestimulation of macrophages by Toll-like receptor (TLR) ligands such as lipopolysaccharide (LPS) purified from E scherichia coli or C. trachomatis L2 prior to infection greatly enhanced secretion of IL-1β from these cells. By using LPS-primed macrophages as a model system, it was determined that IL-1β secretion was dependent on caspase-1, potassium efflux, and the activity of serine proteases. Significantly, chlamydia-induced IL-1β secretion in macrophages required bacterial viability but not growth. Our findings demonstrate that IL-1β secreted by macrophages and neutrophils has important effects in vivo during chlamydial infection. Additionally, prestimulation of macrophages by chlamydial TLR ligands may account for the elevated levels of pro-IL-1β mRNA observed in vivo in this cell type. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1128/iai.00883-09 |
| DOI: |
10.1128/IAI.00883-09 |
| Availability: |
https://doi.org/10.1128/iai.00883-09; https://journals.asm.org/doi/pdf/10.1128/IAI.00883-09 |
| Rights: |
https://journals.asm.org/non-commercial-tdm-license |
| Accession Number: |
edsbas.6FDD1FB1 |
| Database: |
BASE |