1Mobdy HR, 1Manaa WM, 2Nassar M, 3Phillips SM and 1[†]El-Sheikh N.
1Microbiology Department, Faculty of Medicine for Girls, Al Azhar University, 2Pathology Department, Faculty of Medicine, Assuit University; 3Allergy and Immunology Division, School of Medicine, University of Pennsylvania, USA.
The study evaluates the effect of vaccination on the expression of several receptor/ligand pairs of adhesion molecules in an attenuated cercaria vaccine model, during lung and post-lung stages of Schistosoma mansoni migration. The expression of VCAM-1 and ICAM-1 on the vascular endothelial cells and their cognate ligands; VLA-4 and LFA-1, and Mac-1 respectively, on the infiltrating pulmonary leukocytes were assessed. Lung tissues and bronchoalveolar lavage (BAL) cells, were obtained from vaccinated (V), naïve (N), vaccinated/challenged (VC) and naive/challenged (NC) mice groups at days 6,10,14, and 21 after exposure. Cryostat sections and cell smears were stained with immunofluorescence and positive signals were analyzed by image analyzer. The expression of VCAM-1/VLA-4, ICAM-1/LFA-1, and ICAM-1/Mac-1 receptor/ligand pairs increased significantly after vaccination and after challenge infection. The peak time for VCAM-1 and ICAM-1 expression on the vascular endothelial cells was at day 10 and day 6 in the V mice group respectively. At these days, the % expression (mean ± SEM) for VCAM-1 was 3.58+0.53 versus 0.1±0.1 in the V versus N mice groups respectively and 30.1+ 5.20 versus 13.7+4.0 in VC versus NC mice groups respectively (p<0.001). Similarly, the % expression for ICAM-1 was 46.9±3.7, 8.0±1.0, 44.1+9.0, and 25.2+7.1 in V, N, VC, and NC groups respectively (p<0.001). The upregulation in VCAM-1 and ICAM-1 coincided with the upregulation in their counter receptor ligands on the BAL cells. The number of BAL cells expressing VLA-4, LFA-1, and Mac-1 was significantly higher in V than N mice groups (P<0.001), and in VC than NC mice groups (P<0.001). Kinetic studies revealed gradual increase in the intensity of expression per cell throughout the sampling days of each experiment. These findings suggest that multiple adhesion receptors are involved in the protection mechanisms against S. mansoni and that cooperative interactions of VCAM-1 with VLA-4 and of LFA-1 with ICAM-1 and Mac-1 may influence CD4+ T cell interactions that mediate lung phase immunity.