The intercellular adhesion molecule type-1 is required for rapid activation of T helper type 1 lymphocytes that control early acute phase of genital chlamydial infection in mice.
Recent studies in animal models of genital chlamydial disease revealed that early recruitment of dendritic cells and specific T helper type-1 (Th1) cells into the genital mucosae is crucial for reducing the severity of the acute phase of a cervico-vaginal infection and arresting ascending disease. These immune effectors are therefore important for preventing major complications of genital chlamydial infection. Other in vitro studies showed that intercellular adhesion molecule-1 (ICAM-1) plays a role in the antichlamydial action of specific CD4+ and CD8+ T cells. In the present study, we investigated the clinicopathological consequences of ICAM-1 deficiency during chlamydial genital infection in ICAM-1 knockout (ICAM-1KO) mice, and analysed the cellular and molecular immunological bases for any observed pathology or complication. Following a primary genital infection of female ICAM-l-/- and ICAM-1+/+ mice, the intensity of the disease during the first 3 weeks (as assessed by shedding of chlamydiae in the genital tract) was significantly greater in ICAM-1KO mice than in ICAM-1+/+ mice (P < 0.0001), although both ICAM-l-/- and ICAM-1+/+ mice subsequently cleared the primary infection. There was greater ascending disease during the initial stage of the infection, and a higher incidence of tubal disease (hydrosalpinx formation) after multiple infections in ICAM-l-/- mice. Analysis of the cellular and molecular bases for the increased acute and ascending disease in ICAM-l-/- mice revealed that the high affinity of ICAM-1 for leucocyte function antigen type-1 is a property that promotes rapid activation of specific Th1 cells, as well as their early recruitment into the genital mucosa. Moreover, ICAM-1 was more important for naive T-cell activation than primed Th1 cells, although its absence delayed or suppressed immune T-cell activation by at least 50%. Taken together, these results indicated that ICAM-1 is crucial for rapid T-cell activation, early recruitment and control of genitally acquired Chlamydia trachomatis.
Igietseme
J U
JU
Department of Microbiology, Morehouse School of Medicine, Spelman College, Atlanta, GA, USA.
Ananaba
G A
GA
Bolier
J
J
Bowers
S
S
Moore
T
T
Belay
T
T
Lyn
D
D
Black
C M
CM
D000208:Acute Disease; D000704:Analysis of Variance; D000818:Animals; D017951:Antigen Presentation; D002690:Chlamydia Infections / Q000276:immunology* / Q000473:pathology; D002692:Chlamydia trachomatis; D005184:Fallopian Tube Diseases / Q000276:immunology / Q000473:pathology; D005187:Fallopian Tubes / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005831:Genital Diseases, Female / Q000276:immunology* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D013997:Time Factors
D018799:Intercellular Adhesion Molecule-1