Schistosoma mansoni infection induces plasmablast and plasma cell death in the bone marrow and accelerates the decline of host vaccine responses

Abstract

Schistosomiasis is a potentially lethal parasitic disease that profoundly impacts systemic immune function in chronically infected hosts through mechanisms that remain unknown. Given the immunoregulatory dysregulation experienced in infected individuals, this study examined the impact of chronic schistosomiasis on the sustainability of vaccine-induced immunity in both children living in endemic areas and experimental infections in mice. Data show that chronic Schistosoma mansoni infection impaired the persistence of vaccine specific antibody responses in poliovirus-vaccinated humans and mice. Mechanistically, schistosomiasis primarily fostered plasmablast and plasma cell death in the bone marrow and removal of parasites following praziquantel treatment reversed the observed cell death and partially restored vaccine-induced memory responses associated with increased serum anti-polio antibody responses. Our findings strongly suggest a previously unrecognized mechanism to explain how chronic schistosomiasis interferes with an otherwise effective vaccine regimen and further advocates for therapeutic intervention strategies that reduce schistosomiasis burden in endemic areas prior to vaccination.

Helminth infection impacts hematopoiesis

“…In the myeloid lineage, infection preferentially increased the frequency of bone marrow monocytes and eosinophils but not neutrophils or dendritic cells (Figure 1J-M). Infection significantly decreased bone marrow B cell frequency (Figure 1N) in agreement with a recent report (33). The infected spleen had an increased frequency and number of most myeloid lineage cell types (supplemental Figure 1Q-AB).…”

Schistosoma mansoniinfection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses

“…al. recently reported that lower responders to HepB vaccination had lower frequencies of cTfh cells and antibody-secreting plasmablasts (42); and Musaigwa and colleagues describe that S. mansoni infection specifically induces cell death in bone marrow plasmablasts and plasma cells (60). We show in addition to a lower frequency of cTfh cells in individuals with high CAA, a significant increase in activated B cells but a reduction in proliferating (antigen-specific) ASCs, ASCs expressing IgG and IgA, and that IgA + ASCs positively correlate with HepB titers.…”

Prevalence and Clinical Relevance of <i>Schistosoma mansoni</i> Co-Infection with <i>Mycobacterium tuberculosis</i>: A Systematic Literature Review

“…The observation was further supported by Musaigwa et al (2022) that Sch. m infection affects vaccine response again TB infection by inducing deaths of plasmablast and plasma cells in the bone marrow [43].…”