Abstract
Infection with Schistosoma mansoni causes a chronic parasitic disease that progress to severe liver and gastrointestinal damage, and eventually death. During its development into mammalian hosts, immature schistosomula transit through the lung vasculature before they reach the liver to mature into adult worms. A low grade inflammatory reaction is induced during this process. However, molecules that are required for efficient leukocyte accumulation in the lungs of S. mansoni-infected subjects are unknown. In addition, specific leukocyte subsets that mediate pulmonary response during S. mansoni migration through the lung remain to be elucidated. β2 integrins are fundamental regulators of leukocyte trans-endothelial migration and function. Therefore, we investigated their role during experimental schistosomiasis. Mice that express low levels of CD18 (the common β2 integrin subunit) and wild type C57BL/6 mice were subcutaneously infected with S. mansoni cercariae. Cellular profiles of lungs and livers were evaluated in different time points after infection by flow cytometry. Low levels of CD18 affected the accumulation of patrolling Ly6Clow, intermediate Ly6Cinter monocytes, monocyte-derived macrophages and monocyte-derived dendritic cells in the lungs 7 days after infection. This correlated with increased TNF-α levels. Strikingly, low CD18 expression resulted in monocytopenia both in the peripheral blood and bone marrow during acute infection. After 48 days, S. mansoni worm burdens were higher in the hepatic portal system of CD18low mice, which also displayed reduced hepatic accumulation of patrolling Ly6Clow and intermediate Ly6Cinter, but not inflammatory Ly6Chigh monocytes. Higher parasite burden resulted in increased granulomatous lesions in the liver, increased egg deposition and enhanced mortality. Overall, our data point for a fundamental role of CD18 for monocyte hematopoiesis during infection, which promotes an efficient host response against experimental schistosomiasis.
Highlights
Schistosomiasis is a neglected helminthic disease caused by worms of the genus Schistosoma spp. [1]
To investigate whether β2 integrins play a role in lung response during S. mansoni infection, C57BL/6 (WT) mice were initially infected with 80 cercariae
Lung leukocytes from naïve WT mice expressed higher levels of CD11b compared to CD11c, which were significantly elevated 3 and 14 days after S. mansoni infection (Figure 1B)
Summary
Schistosomiasis is a neglected helminthic disease caused by worms of the genus Schistosoma spp. [1]. During the acute phase of schistosomiasis, innate immune cells are activated and predominantly produce cytokines such as TNF-α, IL-2, IL-6, and IL-1β. During S. japonica infection, monocyte-derived dendritic cells (MDCs) produce IL-4 to trigger Th2 responses in the liver [9]. These cells are commonly known as inflammatory DCs, characterized by the surface expression of CD11b+, CD11c+, MHC-II+, CD40+, CD86+, and Ly6Chigh [10]. Seminal studies in mice lead to the important observation that lungs of S. mansoni-infected animals, and not the skin, promote the greatest obstacle for further parasite migration in the vasculature [3, 17]. The dynamics of innate immune cell responses during S. manoni migration through the lung and the possible implications for latter outcomes remain poorly understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
