Mouse strain-dependent chemokine regulation of the genital tract T helper cell type 1 immune response.
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.
Darville
T
T
Department of Pediatric Infectious Diseases, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72202, USA. darvilletonil@uams.edu
Andrews
C W
CW
Sikes
J D
JD
Fraley
P L
PL
Braswell
L
L
Rank
R G
RG
D000818:Animals; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000096:biosynthesis*; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000276:immunology*; D005260:Female; D005831:Genital Diseases, Female / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology*
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D019402:Macrophage Inflammatory Proteins; D016753:Interleukin-10; D007371:Interferon-gamma