Chlamydia trachomatis-induced production of interleukin-1 by human monocytes.
Human diseases caused by the intracellular bacterium Chlamydia trachomatis include genital tract infections and blinding trachoma. Chlamydial infections are characterized by chronic inflammation and scarring, and development of such complications is thought to be immunologically mediated. In this study, we show that coculture of C. trachomatis (serovar L2) with human blood monocytes induced the production of interleukin-1 (IL-1), an important mediator of inflammation, tissue remodeling, and scarring. IL-1 was produced in response to UV-inactivated elementary bodies containing from 0.1 to 50 micrograms of protein per ml, with a maximal response at 5 to 10 micrograms/ml. IL-1 activity was detected by 6 h of incubation and was maximal by 24 h. Peak levels were maintained throughout 96 h of incubation. Rabbit antibody to human IL-1(alpha + beta) effectively neutralized the thymocyte-stimulating activity of the supernatants. The apparent molecular weight of chlamydia-induced IL-1 was 16,000, as determined by gel filtration on a Bio-Gel P-60 column. Isoelectric focusing yielded two peaks of activity, with pIs of 5.5 and 6.9. Neutralization studies with antisera against human IL-1 alpha and IL-1 beta showed that the acidic and neutral peaks corresponded to IL-1 alpha and IL-1 beta, respectively, with IL-1 beta predominating. Heat-killed chlamydiae, which are not internalized by monocytes, were effective IL-1 inducers, indicating that phagocytosis was not required for IL-1 induction. Purified C. trachomatis lipopolysaccharide was also an effective IL-1 inducer, suggesting that the response to intact organisms may be largely a response to chlamydial lipopolysaccharide. Finally, purified chlamydial major outer membrane protein induced low but detectable IL-1 activity.
Rothermel
C D
CD
Department of Medicine, Cornell University Medical College, New York 10021.
Schachter
J
J
Lavrich
P
P
Lipsitz
E C
EC
Francus
T
T
D000906:Antibodies / Q000502:physiology; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology; D001667:Binding, Competitive; D002692:Chlamydia trachomatis / Q000276:immunology*; D002850:Chromatography, Gel; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000276:immunology / Q000302:isolation & purification; D007525:Isoelectric Focusing; D008070:Lipopolysaccharides / Q000502:physiology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D009500:Neutralization Tests; D010587:Phagocytosis; D013601:T-Lymphocytes / Q000276:immunology
D000906:Antibodies; D001425:Bacterial Outer Membrane Proteins; D007106:Immune Sera; D007375:Interleukin-1; D008070:Lipopolysaccharides