Related Experiment Videos
The inflammatory cytokine response to Chlamydia trachomatis infection is endotoxin mediated
R R Ingalls1, P A Rice, N Qureshi
1Maxwell Finland Laboratory for Infectious Diseases, Boston City Hospital, Massachusetts, USA.
Abstract:
Chlamydia trachomatis is a major etiologic agent of sexually transmitted diseases. Although C. trachomatis is a gram-negative pathogen, chlamydial infections are not generally thought of as endotoxin-mediated diseases. A molecular characterization of the acute immune response to chlamydia, especially with regard to the role of its lipopolysaccharide (LPS), remains to be undertaken. We extracted 15 mg of LPS from 5 x 10(12) C. trachomatis elementary bodies (EB) for analysis of structure and biological activity. When methylated lipid A was subjected to high-pressure liquid chromatography followed by mass spectrometry, the majority of the lipid A was found to be pentaacyl. The endotoxin activities of whole C. trachomatis EB and purified LPS were characterized in comparison with whole Salmonella minnesota R595 and with S. minnesota R595 LPS and lipooligosaccharide from Neisseria gonorrhoeae. Both C. trachomatis LPS and whole EB induced the release of tumor necrosis factor alpha from whole blood ex vivo, and C. trachomatis LPS was capable of inducing the translocation of nuclear factor kappa B in a Chinese hamster ovary fibroblast cell line transfected with the LPS receptor CD14. In both assays, however, C. trachomatis was approximately 100-fold less potent than S. minnesota and N. gonorrhoeae. The observation that C. trachomatis is a weak inducer of the inflammatory cytokine response correlates with the clinical observation that, unlike N. gonorrhoeae infection, genital tract infection with C. trachomatis is often asymptomatic. The ability of specific LPS antagonists to completely inhibit the tumor necrosis factor alpha-inducing activity of whole C. trachomatis EB suggests that the inflammatory cytokine response to chlamydia infection may be mediated primarily through LPS. This implies that the role of other surface protein antigens, at least in terms of eliciting the proinflammatory cytokine response, is likely to be minor.
Insights
Chlamydia trachomatis lipopolysaccharide (LPS) weakly induces inflammatory responses, explaining its often asymptomatic infections. This suggests LPS is the primary mediator of chlamydial immune responses.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Chlamydia trachomatis is a major cause of sexually transmitted diseases.
- Despite being gram-negative, chlamydial infections are not typically viewed as endotoxin-mediated.
- The acute immune response to C. trachomatis, particularly the role of its lipopolysaccharide (LPS), requires molecular characterization.
Purpose of the Study:
- To molecularly characterize the acute immune response to C. trachomatis, focusing on the role of its lipopolysaccharide (LPS).
- To analyze the structure and biological activity of C. trachomatis LPS.
- To compare the endotoxin activities of C. trachomatis with other bacterial pathogens.
Main Methods:
- Lipopolysaccharide (LPS) was extracted from C. trachomatis elementary bodies (EB).
- Methylated lipid A was analyzed using high-pressure liquid chromatography and mass spectrometry.
- Endotoxin activities were assessed by measuring tumor necrosis factor alpha release from whole blood and nuclear factor kappa B translocation in a CD14-transfected cell line, comparing C. trachomatis with Salmonella minnesota and Neisseria gonorrhoeae.
Main Results:
- The majority of C. trachomatis lipid A was found to be pentaacylated.
- Both purified C. trachomatis LPS and whole EB induced tumor necrosis factor alpha release and nuclear factor kappa B translocation.
- C. trachomatis LPS and EB were approximately 100-fold less potent than Salmonella and Neisseria gonorrhoeae in inducing these inflammatory responses.
- Specific LPS antagonists inhibited the TNF-alpha-inducing activity of C. trachomatis EB.
Conclusions:
- C. trachomatis is a weak inducer of inflammatory cytokine responses, correlating with its often asymptomatic clinical presentation.
- The lipopolysaccharide (LPS) of C. trachomatis appears to be the primary mediator of the inflammatory cytokine response during chlamydia infection.
- The role of other C. trachomatis surface protein antigens in eliciting a proinflammatory cytokine response is likely minor.