Abstract
For decades, mass drug treatment with praziquantel (PZQ) has been utilized to treat schistosomiasis, yet reinfection and the risk of drug resistance are among the various factors precluding successful elimination of schistosomiasis. Tractable models that replicate “real world” field conditions are crucial to effectively evaluate putative schistosomiasis vaccines. Herein, we describe the cellular immune responses and cytokine expression profiles under field conditions that include prior infection with schistosomes followed by treatment with PZQ. Baboons were exposed to Schistosoma mansoni cercariae through trickle infection over 5 weeks, allowed for chronic disease to develop, and then treated with PZQ. Peripheral blood mononuclear cells (PBMCs) were monitored for cellular immune response(s) at each disease stage and PZQ therapy. After initial infection and during chronic disease, there was an increase in non-classical monocytes, NK and NKT cells while the CD4:CD8 T cell ratio inverted from a 2:1 to 1:2.5. The cytokine expressions of PBMCs after trickle infections were polarized more toward a Th2 response with a gradual increase in Th1 cytokine expression at chronic disease stage. Following PZQ treatment, with the exception of an increase in B cells, immune cell populations reverted back toward naïve levels; however, expression of almost all Th1, Th2, and Th17 cytokines was significantly increased. This preliminary study is the first to follow the cellular immune response and cytokine expression profiles in a non-human primate model simulating field conditions of schistosomiasis and PZQ therapy, providing a promising reference in predicting the immune response to future vaccines for schistosomiasis.
Highlights
Parasites have coevolved with their hosts to maintain a tenuous balance between propagation of the parasite life cycle and host immunopathology
Peripheral blood was collected during each stage of disease development and after completion of PZQ therapy and myeloid and lymphoid cell lineages were assessed—these data demonstrate the changes in the cellular immune response following repeated trickle infection, disease progression and subsequent PZQ treatment (Figure 1B)
We did not observe any significant changes in the levels of classical monocytes but the population of intermediate monocytes had a moderate decrease from trickle infection to PZQ treatment (p = 0.0571; Supplementary Figure 2)
Summary
Parasites have coevolved with their hosts to maintain a tenuous balance between propagation of the parasite life cycle and host immunopathology. Praziquantel (PZQ), a drug co-developed by Bayer AG and Merck KGaA in the 1970s, has been implemented in many national programs as an integral component of control and elimination strategies and is the drug of choice for the treatment of schistosomiasis (Olveda et al, 2016; Bergquist et al, 2017; Gower et al, 2017; Kabore et al, 2017; Kimani et al, 2018). PZQ is considered non-toxic and highly effective against adult schistosomes, it is unable to kill developing schistosomes and the individual remains susceptible to subsequent infections. The development of an effective vaccine against schistosomiasis is crucial to complement existing control strategies for long-term disease control and, subsequently, elimination
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