Scavenger receptors mediate increased uptake of irradiated T.gondii extracts by J774 macrophages

Author(s)

da Costa, Andrea ; de Carvalho, Camila Aparecida ; do Nascimento, Nanci ; de Andrade Jr, Heitor Franco

• Document type: Journal article
• Source: International Journal of Radiation Biology; v. 99, n. 10, p. 11-pg., 2023-03-10.

Abstract

PurposeProtein extracts developed increased immunogenicity without the aid of adjuvants after gamma irradiation. Gamma irradiation of snake venom increased antivenin production by detoxification and enhanced immunity, probably due preferential uptake of irradiated venoms by macrophage scavenger receptors. We studied this uptake of irradiated soluble Toxoplasma gondii extract (STag) by the J774 macrophage cell line similar to antigen presenting cells.Material And MethodsWe labeled STag by biosynthesis in living tachyzoites with radioactive amino acids before purification and irradiation or by adding labels as biotin or fluorescein in stored STag, for quantitative studies or subcellular distribution visualization.ResultsThere was enhanced binding and uptake of irradiated STag into the cells compared to non-irradiated STag. Using fluorescein labeled antigens and morphological assays, we confirmed that cells avidly ingested both native and irradiated proteins but native STag were digested after ingestion while irradiated proteins remained in the cell, suggesting diverse intracytoplasmic pathways. Native or irradiated STag present the same in vitro sensitivity to three types of peptidases. Inhibitors of scavenger receptors (SRs) such as Dextran sulfate (SR-A1 blocker) or Probucol (SR-B blocker) affect the specific uptake of irradiated antigens, suggesting its association with enhanced immunity.ConclusionsOur data suggests that cell SRs recognize irradiated proteins, mainly SRs for oxidized proteins, leading to antigen uptake by an intracytoplasmic pathway with fewer peptidases that prolongs presentation to nascent major histocompatibility complex I or II and enhances immunity by better antigen presentation. (AU)

• FAPESP's process: 13/04676-9 - Flow cytometry and fluorimetry in diseases caused by protozoa
• Grantee: Heitor Franco de Andrade Junior
• Support Opportunities: Regular Research Grants