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Isolation of Lymphocytes from Mouse Genital Tract Mucosa
Published on: September 3, 2012
Mouse strain-dependent chemokine regulation of the genital tract T helper cell type 1 immune response
T Darville1, C W Andrews, J D Sikes
1Department of Pediatric Infectious Diseases, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72202, USA. darvilletonil@uams.edu
Abstract:
Vaginal infection with the mouse pneumonitis agent of Chlamydia trachomatis (MoPn) produces shorter courses of infection in C57BL/6 and BALB/c mice than in C3H/HeN mice, while C57BL/6 mice are more resistant to oviduct pathology. A robust Th1 response is extremely important in host defense against chlamydia. In this study we examined gamma interferon (IFN-gamma), interleukin 10 (IL-10), and the T-cell-regulatory chemokines macrophage inflammatory protein-1alpha (MIP-1alpha) and monocyte chemoattractant protein-1 (MCP-1) to determine if differences in these responses were associated with the differential courses of infection seen in these three strains of mice. Increased and prolonged IFN-gamma responses and lower IL-10 responses were observed in the C57BL/6 strain compared to BALB/c and C3H. Examination of genital tract chemokines revealed a marked predominance of MIP-1alpha over MCP-1 only in the C57 strain. Thus, a pattern of high MIP-1alpha and low MCP-1 levels during the first week of infection is associated with an increased Th1 response and a shorter, more benign chlamydial infection. Inhibition of the MCP-1 response in C3H mice increased their later T-cell production of IFN-gamma but decreased their early IFN-gamma response and had no effect on the course or outcome of infection. Inhibition of MCP-1 is not beneficial in chlamydial infection because of its pleiotropic effects.
Insights
Mice infected with Chlamydia trachomatis (MoPn) show varied responses. A strong Th1 immune response, marked by high macrophage inflammatory protein-1alpha (MIP-1alpha) and low monocyte chemoattractant protein-1 (MCP-1), correlates with shorter, milder infections.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Chlamydia trachomatis (MoPn) infection in mice exhibits strain-dependent differences in infection duration and oviduct pathology.
- A strong Th1 immune response is critical for host defense against chlamydial infections.
Purpose of the Study:
- To investigate if differential immune responses, specifically gamma interferon (IFN-gamma), interleukin 10 (IL-10), MIP-1alpha, and MCP-1, correlate with observed variations in chlamydial infection courses across different mouse strains.
- To elucidate the role of specific chemokines in modulating the immune response to Chlamydia trachomatis.
Main Methods:
- Comparative analysis of IFN-gamma, IL-10, MIP-1alpha, and MCP-1 levels in C57BL/6, BALB/c, and C3H/HeN mice during Chlamydia trachomatis infection.
- Assessment of oviduct pathology and infection duration across the studied mouse strains.
- Inhibition studies of MCP-1 to evaluate its impact on IFN-gamma production and infection outcomes.
Main Results:
- C57BL/6 mice displayed higher and more prolonged IFN-gamma responses and lower IL-10 responses compared to BALB/c and C3H mice.
- A distinct pattern of high MIP-1alpha relative to MCP-1 was observed in C57BL/6 mice during the initial week of infection.
- Inhibition of MCP-1 in C3H mice altered IFN-gamma kinetics but did not improve the infection course or outcome, highlighting its complex role.
Conclusions:
- A host immune profile characterized by elevated MIP-1alpha and suppressed MCP-1 during early infection is associated with a robust Th1 response and a more favorable chlamydial infection outcome.
- MCP-1 inhibition is not a universally beneficial strategy for managing chlamydial infections due to its pleiotropic effects on the immune system.

