Infection with Schistosoma mansoni causes a neglected chronic parasitic disease affecting 200 million people around the world. During its development into mammalian hosts, immature schistosomula transit through the lung vasculature before they reach the liver to mature into adult worms. The inflammatory response to infection leads the mononuclear and polymorphonuclear cell recruitment that eliminate a significant number of cercariae. The traffick of such cells to affected tissues depends on chemokines, bioactive lipids, and molecules involved in cellularadhesion. ²2 integrins are fundamental regulators of leukocyte trans-endothelial migration and function. Recently, we demonstrated an essential role of CD18 for hematopoiesis of different monocyte subsets (Ly6Chigh, Ly6Cinter and Ly6Clow) in the bone marrow. CD18 also regulates the accumulation of patrolling monocytes (Ly6Clow) in the lung during acute infection with S. mansoni, correlating with resistance during the chronic phase in liver. However, the molecular mechanisms by which CD18 coordinates monocyte hematopoiesis and/or monocyte survival, and function of these cells during schistosomiasis remain poorly elucidated. In this project, we propose to investigate further the role of CD18 on the generation of monocytes during experimental schistosomiasis and determine the function of patrolling monocytes. These cells depend on the signaling from the chemokine receptor CX3CR1 for survival and surveillance of the endothelium. Preliminary data indicate that mice expressing non-functional CX3CR1 (CX3CR1gfp/gfp) and infected with S. mansoni exhibit significantly reduced frequency of patrolling monocytes in the bone marrow and peripheral blood after 7 days of infection. These data indicate that both CX3CR1 and CD18 are crucial for patrolling monocytes during experimental infection with S. mansoni and they may act in parallel on the generation, development or maturation of monocytes. This project presents great potential to uncover molecular mechanisms that are necessary to generate monocytes and shell contribute to the rational of new therapeutic strategies to helminthic infections.
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