Leveraging the Townes mice to study interactions between sickle cell disease and schistosome (human blood fluke worm) infection

Authors

• JPK Mukendi
• COS Souza
• O Kamenyeva
• J Kabat
• S Kamimura
• M Smith
• ZMN Quezado
• P Loke

Abstract

Background: Sickle cell disease (SCD) is an inherited hematologic disease due to a single nucleotide mutation in the beta chain of human hemoglobin (Hb) that produces defective Hb called HbS. Hypoxic conditions make HbS polymerize, leading to red blood cells sickling and hemolyzing. Most disease cases are in sub-Saharan Africa, where schistosomiasis, a worm infection causing severe inflammation and anemia, is also endemic. However, possible interactions between SCD and schistosomiasis remain largely unknown. This study used the Townes mouse model of SCD to determine the interactions between SCD and schistosome infection.
Methods: Townes mice were infected with Schistosoma mansoni for eight weeks. Hematologic parameters were analyzed before and after infection; histology of the liver and spleen and S. mansoni egg counts were performed. Liver microcirculation and tissue were also intravitally imaged.
Results: S. mansoni infection increased granulocytes (neutrophils, p=0.0005; eosinophils, p<0.0001; basophils, p<0.0001) and monocyte (p<0.0001) counts in peripheral blood but did not worsen anemia in HbSS mice (RBC, p=0.3382; Hb, p=0.7000, Hct, p=0.4590). However, it significantly decreased hepatic hemosiderosis (p<0.0001) in HbSS mice. On the contrary, SCD did not affect peri-oval granuloma formation in the liver of infected mice but caused a slight reduction of S. mansoni egg burden.
Conclusion: Townes mice are susceptible to S. mansoni infection and, therefore, constitute a good model for mechanistically characterizing the interactions between SCD and schistosomiasis. This study stands as a proof of concept for the use of Townes mice in the study of worm infections in SCD and warrants further investigations.

Scientific Focus Area: Microbiology and Infectious Diseases

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