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

Infection and Immunity
|November 14, 2001
PubMed

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.