Dynamics of host immune response development during Schistosoma mansoni infection

Abstract

Schistosomiasis is a disease of global significance, with severity and pathology directly related to how the host responds to infection. The immunological narrative of schistosomiasis has been constructed through decades of study, with researchers often focussing on isolated time points, cell types and tissue sites of interest. However, the field currently lacks a comprehensive and up-to-date understanding of the immune trajectory of schistosomiasis over infection and across multiple tissue sites. We have defined schistosome-elicited immune responses at several distinct stages of the parasite lifecycle, in three tissue sites affected by infection: the liver, spleen, and mesenteric lymph nodes. Additionally, by performing RNA-seq on the livers of schistosome infected mice, we have generated novel transcriptomic insight into the development of schistosome-associated liver pathology and fibrosis across the breadth of infection. Through depletion of CD11c+ cells during peak stages of schistosome-driven inflammation, we have revealed a critical role for CD11c+ cells in the co-ordination and regulation of Th2 inflammation during infection. Our data provide an updated and high-resolution account of how host immune responses evolve over the course of murine schistosomiasis, underscoring the significance of CD11c+ cells in dictating host immunopathology against this important helminth infection.

Increased hepatic interleukin-1, arachidonic acid, and reactive oxygen species mediate the protective potential of peptides shared by gut cysteine peptidases against Schistosoma mansoni infection in mice

“…mansoni maturation [ 28 ]. The most striking finding ( P < 0.01) involved increase in IL-17, likely responsible for the changes in cellular infiltration in the liver as early as 4 wks PI, compared to naïve mice, described by Costain et al [ 29 ]. Despite the dramatic increase reported by Costain et al [ 29 ] in numbers of hepatic eosinophils and macrophages in 4 wks-infected mice, no changes in ARA or ROS hepatic content was recorded in 23 days-infected mice, compared to naïve controls.…”

“…The most striking finding ( P < 0.01) involved increase in IL-17, likely responsible for the changes in cellular infiltration in the liver as early as 4 wks PI, compared to naïve mice, described by Costain et al [ 29 ]. Despite the dramatic increase reported by Costain et al [ 29 ] in numbers of hepatic eosinophils and macrophages in 4 wks-infected mice, no changes in ARA or ROS hepatic content was recorded in 23 days-infected mice, compared to naïve controls. The adjuvant used, alum (aluminum hydroxide, 130 μg/injection) failed to impact challenge worms’ survival or fecundity, associated with induction of significant ( P < 0.05 to P < 0.005) reduction in liver cytokines, including IL-17, ARA, and ROS content when compared to levels recorded in naïve or unimmunized infected mice.…”

Schistosomiasis Mansoni-Recruited Eosinophils: An Overview in the Granuloma Context

“…Oviposition can further stimulate more pronounced blood eosinophilia, as noted in patients with acute infection [ 5 , 10 , 37 ]. Tissue eosinophilia is found during the early stages of granuloma formation within the inner perimeter of circumoval inflammation, as detected by immunolabeling with Siglec-F [ 49 ], an eosinophil surface receptor considered a marker for this cell [ 50 , 51 ]. The chronic phase is generally associated with reduced blood eosinophilia, since studies on the chronic phase of S. mansoni infection in humans have shown eosinophilia in less than 50% of subjects [ 52 , 53 ].…”

“…CD4+ T lymphocytes release IL-5, a key cytokine that attracts eosinophils to the inflammatory tissue sites and also contributes to increased blood eosinophilia in association with granulocyte-macrophage colony-stimulating factor (GM-CSF) under a Th2 environment [ 4 , 9 , 27 , 67 , 68 , 69 ]. Interestingly, the depletion of CD11c, a marker for dendritic cells, dramatically altered granuloma and hepatic cellularity, leading to decreased numbers of eosinophils and T cells [ 49 , 70 ].…”

“…Matrix metalloproteinase 9 (MMP9), a protein produced by neutrophils and involved in modulation processes of hematopoietic function, is also produced within the granuloma [ 75 ]. Finally, another recent study shows that even liver cells from infected mice have a greater potential to produce IL-5 as early as week 4 of infection, which could support not only the rapid recruitment of eosinophils during granuloma initiation and development [ 49 ] but also the local eosinophil differentiation. Altogether, the granuloma microenvironment is considered a niche favorable for eosinophil differentiation and maturation, but future studies are needed for a better understanding of these events.…”