title: Differential regulation of inflammatory cytokine secretion by human dendritic cells upon Chlamydia trachomatis infection.
abstract: Chlamydia trachomatis is an obligate intracellular gram-negative bacterium responsible for a wide spectrum of diseases in humans. Both genital and ocular C. trachomatis infections are associated with tissue inflammation and pathology. Dendritic cells (DC) play an important role in both innate and adaptive immune responses to microbial pathogens and are a source of inflammatory cytokines. To determine the potential contribution of DC to the inflammatory process, human DC were infected with C. trachomatis serovar E or L2. Both C. trachomatis serovars were found to infect and replicate in DC. Upon infection, DC up-regulated the expression of costimulatory (B7-1) and cell adhesion (ICAM-1) molecules. Furthermore, chlamydial infection induced the secretion of interleukin-1beta (IL-1beta), IL-6, IL-8, IL-12p70, IL-18, and tumor necrosis factor alpha (TNF-alpha). The mechanisms involved in Chlamydia-induced IL-1beta and IL-18 secretion differed from those of the other cytokines. Chlamydia-induced IL-1beta and IL-18 secretion required infection with viable bacteria and was associated with the Chlamydia-induced activation of caspase-1 in infected host cells. In contrast, TNF-alpha and IL-6 secretion did not require that the Chlamydia be viable, suggesting that there are at least two mechanisms involved in the Chlamydia-induced cytokine secretion in DC. Interestingly, an antibody to Toll-like receptor 4 inhibited Chlamydia-induced IL-1beta, IL-6, and TNF-alpha secretion. The data herein demonstrate that DC can be infected by human C. trachomatis serovars and that chlamydial components regulate the secretion of various cytokines in DC. Collectively, these data suggest that DC play a role in the inflammatory processes caused by chlamydial infections.
authors.affiliation: Corixa Corporation, 1900 9th Ave., Suite 1100, Seattle, WA 98101, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Gervassi
authors.forename: Mark R
authors.initials: MR
authors.lastname: Alderson
authors.forename: Robert
authors.initials: R
authors.lastname: Suchland
authors.forename: Jean François
authors.initials: JF
authors.lastname: Maisonneuve
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Grabstein
authors.forename: Peter
authors.initials: P
authors.lastname: Probst
mesh_terms: D020170:Caspase 1 / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000472:pathogenicity*; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000382:microbiology / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D007375:Interleukin-1; D020382:Interleukin-18; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D020170:Caspase 1