Chemokine and chemokine receptor dynamics during genital chlamydial infection.

Abstract

Current design strategies for vaccines against certain microbial pathogens, including Chlamydia trachomatis, require the induction and targeting of specific immune effectors to the local sites of infection known as the mucosal effector sites. Chemokines and their receptors are important mediators of leukocyte trafficking and of the controlled recruitment of specific leukocyte clonotypes during host defense against infections and during inflammation. We analyzed the dynamics of chemokine and chemokine receptor expression in genital mucosae during genital chlamydial infection in a murine model to determine how these molecular entities influence the development of immunity and the clearance of infection. A time course study revealed an increase of up to threefold in the levels of expression of RANTES, monocyte chemotactic protein 1 (MCP-1), gamma-interferon-inducible protein 10 (IP-10), macrophage inflammatory protein 1alpha (MIP-1alpha), and intercellular adhesion molecule type 1 (ICAM-1) after genital infection with the C. trachomatis agent of mouse pneumonitis. Peak levels of expression of RANTES, MCP-1, and MIP-1alpha occurred by day 7 after primary infection, while those of IP-10 and ICAM-1 peaked by day 21. Expression levels of these molecules decreased by day 42 after primary infection, by which time all animals had resolved the infection, suggesting an infection-driven regulation of expression. A rapid upregulation of expression of these molecules was observed after secondary infection. The presence of cells bearing the chemokine receptors CCR5 and CXCR3, known to be preferentially expressed on Th1 and dendritic cells, was also synchronous with the kinetics of immune induction in the genital tract and clearance of infection. Results demonstrated that genital chlamydial infection is associated with a significant induction of chemokines and chemokine receptors that are involved in the recruitment of Th1 cells into the site of infection. Future studies will focus on how selective modulation of chemokines and their receptors can be used to optimize long-term immunity against CHLAMYDIA:

• Authors: Tesfaye Belay, Francis O Eko, Godwin A Ananaba, Samera Bowers, Terri Moore, Deborah Lyn, Joseph U Igietseme
• Journal: Infection and immunity (Infect Immun) Vol. 70 Issue 2 Pg. 844-50 (Feb 2002) ISSN: 0019-9567 [Print] United States
• PMID: 11796619 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Chemokine CCL2
• Chemokine CCL3
• Chemokine CCL4
• Chemokine CCL5
• Chemokine CXCL10
• Chemokines
• Chemokines, CXC
• Cxcr3 protein, mouse
• Macrophage Inflammatory Proteins
• Receptors, CCR5
• Receptors, CXCR3
• Receptors, Chemokine
• Intercellular Adhesion Molecule-1

Topics

• Animals
• Chemokine CCL2 (genetics)
• Chemokine CCL3
• Chemokine CCL4
• Chemokine CCL5 (genetics)
• Chemokine CXCL10
• Chemokines (genetics)
• Chemokines, CXC (genetics)
• Chlamydia Infections (immunology)
• Chlamydia trachomatis (immunology)
• Disease Models, Animal
• Female
• Gene Expression
• Gene Expression Profiling
• Genital Diseases, Female (immunology)
• Intercellular Adhesion Molecule-1 (genetics)
• Kinetics
• Macrophage Inflammatory Proteins (genetics)
• Mice
• Mice, Inbred BALB C
• Receptors, CCR5 (genetics)
• Receptors, CXCR3
• Receptors, Chemokine (genetics)