Protozoology Laboratory, Instituto de Medicina Tropical de São Paulo and Department Pathology, School of Medicine, Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 470, 1St Floor, São Paulo, SP, CEP 05403-000, Brazil.
Parasitol Res. 2023 Jun;122(6):1283-1291. doi: 10.1007/s00436-023-07828-0. Epub 2023 Mar 29.
Experimental toxoplasmosis is an excellent model for adaptive immune response. Gamma-irradiated tachyzoites or soluble tachyzoite antigen extracts (STag) induce protection against experimental toxoplasmosis in mice. Scavenger receptors recognize irradiated proteins, promote their entry into cells, and lead to antigen presentation. CD36 is a specific scavenger receptor involved in intracellular transport of free fatty acid (FFA), cellular recycling, and intracellular trafficking in lipid rafts outside the lysosomal pathways. CD36 is also associated with an altered immune response, as CD36 mice presented some immune defects in the cyst-forming Toxoplasma gondii. We studied T. gondii infection in CD36 mice, naïve or immunized, with irradiated T. gondii STags by investigating protection, antibody production, and primed macrophage transplantation. CD36 mice presented no resistance against the viable RH tachyzoites, even after immunization with gamma-irradiated STags that protected wild-type mice. The animals presented poor humoral responses to both immunogens despite adequate levels of serum immunoglobulins. CD36 mice failed to induce protection against virulent T. gondii infection with inadequate antibody production or an innate response. Irradiated antigens failed to induce antibodies in CD36 mice and only produced adequate levels of immunoglobulin G when transplanted with irradiated STag-primed wild-type macrophages. The CD36 pathway is necessary for humoral response against the irradiated antigen; however, several other pathways are also involved in mounting a humoral response against any antigen. CD36 is a multipurpose molecule for FFA and lipid transport, as well as for the immune response, and gamma radiation mimics the innate response by targeting irradiated antigens of this pathway.
实验性弓形体病是适应性免疫反应的极佳模型。γ 射线辐照速殖子或可溶性速殖子抗原提取物（STag）可诱导小鼠对实验性弓形体病产生保护作用。清道夫受体识别辐照蛋白，促进其进入细胞，并导致抗原呈递。CD36 是一种参与游离脂肪酸（FFA）细胞内转运、细胞循环和溶酶体途径外脂质筏内细胞内运输的特异性清道夫受体。CD36 还与改变的免疫反应有关，因为 CD36 小鼠在形成孢囊的弓形虫中表现出一些免疫缺陷。我们研究了 CD36 小鼠和未免疫或用辐照的弓形虫 STag 免疫的 CD36 小鼠中的弓形虫感染，通过研究保护、抗体产生和被激活的巨噬细胞移植来研究。即使在用 γ 射线辐照 STag 免疫后，CD36 小鼠也不能抵抗活 RH 速殖子，而野生型小鼠则受到保护。尽管血清免疫球蛋白水平适当，但这些动物对两种免疫原的体液反应都很差。CD36 小鼠未能通过产生不足的抗体或先天反应来诱导对强毒弓形虫感染的保护。辐照抗原不能在 CD36 小鼠中诱导抗体产生，只有在用辐照 STag 激活的野生型巨噬细胞移植时才会产生足够水平的免疫球蛋白 G。CD36 途径是针对辐照抗原产生体液反应所必需的；然而，其他几个途径也参与了针对任何抗原产生体液反应。CD36 是 FFA 和脂质转运以及免疫反应的多用途分子，γ 辐射通过靶向该途径的辐照抗原模拟先天反应。
