Paraquat Preferentially Induces Apoptosis of Late Stage Effector Lymphocyte and Impairs Memory Immune Response in Mice

Abstract

Paraquat (PQ) is a toxic non-selective herbicide. To date, the effect of PQ on memory immune response is still unknown. We investigated the impact of PQ on memory immune response. Adult C57BL/6 mice were subcutaneously injected with 2 mg/kg PQ, 20 mg/kg PQ or vehicle control every three days for two weeks. A single injection of keyhole limpet hemocyanin (KLH) at day four after the initial PQ treatment was used to induce a primary immune response; a second KLH challenge was performed at three months post the first KLH immunization to induce a secondary immune response. In steady state, treatment with 20 mg/kg PQ reduced the level of serum total IgG, but not that of IgM; treatment with 20 mg/kg PQ decreased the number of effector and memory lymphocytes, but not naïve or inactivated lymphocytes. During the primary immune response to KLH, treatment with 20 mg/kg PQ did not influence the proliferation of lymphocytes or expression of co-stimulatory molecules. Instead, treatment with 20 mg/kg PQ increased the apoptosis of lymphocytes at late stage, but not early stage of the primary immune response. During the secondary immune response to KLH, treatment with 20 mg/kg PQ reduced the serum anti-KLH IgG and KLH-responsive CD4 T cells and B cells. Moreover, effector or activated lymphocytes were more sensitive to PQ-induced apoptosis in vitro. Treatment with 2 mg/kg PQ did not impact memory immune response to KLH. Thus, treatment with 20 mg/kg PQ increased apoptosis of late stage effector cells to yield less memory cells and thereafter impair memory immune response, providing a novel understanding of the immunotoxicity of PQ.

Common contributing factors to COVID-19 and inflammatory bowel disease

“…ID: “treatment with 20 mg/kg PQ increased apoptosis of late stage effector cells to yield less memory cells and thereafter impair memory immune response,” [ 165 ]…”

Paraquat Modulates Immunological Function in Bone Marrow-Derived Macrophages

“…Moreover, PQ impairs phagocytic activity of monocytes and granulocytes (Jang et al 2015), and induces apoptosis of mature CD4 T cells and B cells during a primary immune response. Thus, several studies mentioned above have shown that innate and adaptive immune cell functions were modulated after PQ exposure (Shao et al 2019). Likewise, PQ also has in uence on ROS production in human neural progenitor cells and increased lung malondialdehyde (MDA) level (Chang et al 2013;Toygar et al 2015).…”

Endoplasmic reticulum stress-related neuroinflammation and neural stem cells decrease in mice exposure to paraquat

“…Although some studies suggested that PQ might increase the apoptosis of cells 4 , no increased apoptosis was observed in our study. It seems that various factors, including the dose of PQ and time of PQ exposure, may significantly influence the PQ effect 34 . The highest dose of PQ in our study was 20 mg/kg 35 , slightly higher than other studies 36 , but the mice in our study were injected with PQ only twice with 1 wk apart.…”