The anthelmintic drug praziquantel promotes human Tr1 differentiation

Abstract

Praziquantel (PZQ) is an anthelminthic human and veterinary drug used to treat trematode and cestode worms. Changes in immune responses have been demonstrated in humans following curative PZQ treatment of schistosome infections. These changes have been attributed to the removal of immunosupressive worms and immune responses to parasite antigens exposed from dying worms. To date, there has been no study investigating the potential direct effect of PZQ on the host immune cells. Herein, we analyzed the effect of PZQ on human CD4+ T cells classically costimulated by CD3/CD28 or costimulated by the complement regulator CD46 to induce Type 1 regulatory T cells (Tr1). Our results show that PZQ enhanced T‐cell proliferation, increased secretion of IL‐17 and IL‐10 but had no effect on secretion of GM‐CSF or IFNγ. Moreover, PZQ increased the coexpression of CD49b and LAG‐3, a hallmark of Tr1 cells, suggesting increased Tr1 differentiation. Indeed, supernatants from PZQ‐treated cells were able to decrease bystander T‐cell activation, and this was partly reduced when blocking IL‐10. Hence, our study demonstrates that PZQ directly modulates human T‐cell activation and promotes Tr1 differentiation, suggesting that PZQ may have immunomodulatory functions in parasite‐unrelated human inflammatory diseases.

Elucidation of Cellular Responses in Non-human Primates With Chronic Schistosomiasis Followed by Praziquantel Treatment

“…Conditions such as HIV (Joseph et al, 2004b), coinfection with whipworm (our unpublished data show increased Schistosoma egg-induced hepatopathology during co-infection with Trichuris), malnutrition (Scrimshaw and SanGiovanni, 1997), and others can affect vaccine efficacy. PZQ treatment, discounting the release of parasite antigens, may intrinsically be immunomodulatory (Eyoh et al, 2019). To our knowledge, this study is the first to report the cellular immune response in a non-human primate model of schistosomiasis using multiple trickle infections and subsequent chemotherapy with PZQ.…”

The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities

“…Moreover, two subsets of Foxp3 − Tregs have been discovered with suppressor functions: type 1 Treg (Tr1) and Th3 cells differentiate from peripheral naive CD4 + T cells ( 16 , 23 ). As opposed to tTregs, Th3 and Tr1 suppressive properties are contact independent and is largely relying on cytokines including IL-10 and transforming growth factor- β (TGF- β ) ( 24 ) ( Figure 2 ).…”

The Yin and Yang of Type 1 Regulatory T Cells: From Discovery to Clinical Application

“…The discovery of LAG3 and CD49b expressed on both murine and human memory CD4 + Tr1 cells enabled the isolation and characterization of Tr1 populations from peripheral blood of healthy donors (10). Since then, many other studies confirmed the expression of these proteins on murine (21)(22)(23)(24)(25)(26)(27)(28)(29), non-human primate (30) and human (18,(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44) Tr1 cell populations.…”