Protective human IgE responses are promoted by comparable life-cycle dependent Tegument Allergen-Like protein expression in Schistosoma haematobium and Schistosoma mansoni infection

Schistosoma haematobium is the most prevalent of the human-infecting schistosome species, causing significant morbidity in endemically exposed populations. Despite this, it has been relatively understudied compared to its fellow species, S. mansoni. Here we provide the first comprehensive characterization of the S. haematobium Tegument Allergen-Like protein family, a key protein family directly linked to protective immunity in S. mansoni infection. Comparable with observations for S. mansoni, parasite phylogenetic analysis and relative gene expression combined with host serological analysis support a cross-reactive relationship between S. haematobium TAL proteins, exposed to the host immune system as adult worms die, and closely related proteins, exposed during penetration by the infecting cercarial and early schistosomulae stages. Specifically, our results strengthen the evidence for host immunity driven by cross-reactivity between family members TAL3 and TAL5, establishing it for the first time for S. haematobium infection. Furthermore, we build upon this relationship to include the involvement of an additional member of the TAL protein family, TAL11 for both schistosome species. Finally, we show a close association between experience of infection and intensity of transmission and the development of protective IgE responses to these antigens, thus improving our knowledge of the mechanisms by which protective host immune responses develop. This knowledge will be critical in understanding how control efforts such as mass drug administration campaigns influence the development of host immunity and subsequent patterns of infection and disease within endemic populations. Author Summary S. haematobium is the most prevalent of the human infecting schistosomes. Along with S. mansoni, it is responsible for the majority of schistosomiasis cases that are borne by the populations of sub-Saharan Africa, where the global burden of this infection is centered. Here, we provide insight into the IgE antibody response that protects against these infections. Through utilization of in silico analysis and transcriptional studies of parasite life stages, in combination with immuno-epidemiological studies, we explore the relationship between host immune protection and a parasite protein family named the Tegument Allergen-Like (TAL) proteins. Our results show that several members of the TAL protein family are important in host protection to both these major schistosome species. For the first time we demonstrate that a progressive cross-reactive TAL-IgE response occurs against S. haematobium, similar to that previous observed in S. mansoni infection. We additionally expand upon previous knowledge for S. mansoni, identifying further complexity in the cross-reactive relationship between TAL family members, providing evidence of a key role for family member TAL11 in induction of the protective host immune response.