title: Critical role for interleukin-1beta (IL-1beta) during Chlamydia muridarum genital infection and bacterial replication-independent secretion of IL-1beta in mouse macrophages.
abstract: Recent findings have implicated interleukin-1beta (IL-1beta) as an important mediator of the inflammatory response in the female genital tract during chlamydial infection. But how IL-1beta 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-1beta expression during a chlamydial genital infection. In the present study, IL-1beta(-/-) mice exhibited delayed chlamydial clearance and decreased frequency of hydrosalpinx compared to wild-type (WT) mice, implying an important role for IL-1beta both in the clearance of infection and in the mediation of oviduct pathology. At the peak of IL-1beta secretion in WT mice, the major producers of IL-1beta in vivo are F4/80(+) macrophages and GR-1(+) neutrophils, but not CD45(-) epithelial cells. Although elicited mouse macrophages infected with Chlamydia muridarum in vitro secrete minimal IL-1beta, in vitro prestimulation of macrophages by Toll-like receptor (TLR) ligands such as lipopolysaccharide (LPS) purified from Escherichia coli or C. trachomatis L2 prior to infection greatly enhanced secretion of IL-1beta from these cells. By using LPS-primed macrophages as a model system, it was determined that IL-1beta secretion was dependent on caspase-1, potassium efflux, and the activity of serine proteases. Significantly, chlamydia-induced IL-1beta secretion in macrophages required bacterial viability but not growth. Our findings demonstrate that IL-1beta 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-1beta mRNA observed in vivo in this cell type.
authors.affiliation: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Prantner
authors.forename: Toni
authors.initials: T
authors.lastname: Darville
authors.forename: James D
authors.initials: JD
authors.lastname: Sikes
authors.forename: Charles W
authors.initials: CW
authors.lastname: Andrews
authors.forename: Helmut
authors.initials: H
authors.lastname: Brade
authors.forename: Roger G
authors.initials: RG
authors.lastname: Rank
authors.forename: Uma M
authors.initials: UM
authors.lastname: Nagarajan
mesh_terms: D000818:Animals; D002690:Chlamydia Infections / Q000276:immunology* / Q000382:microbiology; D023502:Chlamydia muridarum / Q000276:immunology*; D015169:Colony Count, Microbial; D005187:Fallopian Tubes / Q000473:pathology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D053583:Interleukin-1beta / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology
chemical_list: D053583:Interleukin-1beta