Vellozo Natália S, Matos-Silva Thayane C, Lopes Marcela F
Laboratório de Biologia Imunitária George DosReis, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Front Immunol. 2025 Aug 7;16:1595954. doi: 10.3389/fimmu.2025.1595954. eCollection 2025.
Macrophage plasticity is remarkable, and recent studies have opened new prophylactic and therapeutic avenues for immunomodulation of macrophage phenotypes in inflammatory and infectious diseases. During infections caused by the pathogenic protozoans spp. and , susceptibility to disseminated or chronic infections and/or the development of inflammatory diseases depend on the balance between protective immunity mediated by macrophages and anti-inflammatory responses. Here, we will discuss strategies that exploit macrophage plasticity towards the extreme proinflammatory M1 or pro-infection M2 phenotypes to prevent the establishment of disseminated and chronic infection or to temper parasite-driven inflammatory responses. Immunomodulation of macrophage phenotypes has been tested in experimental models of protozoan infections through pharmacological approaches, synergy between pro-M1 cytokines, and targeting of pro-M2 macrophage functions, such as efferocytosis. We will address the cellular and molecular mechanisms underlying strategies designed to redirect macrophage activation towards M1 and M2 phenotypes, as well as the challenges and open questions.
巨噬细胞的可塑性十分显著，近期的研究为炎症和感染性疾病中巨噬细胞表型的免疫调节开辟了新的预防和治疗途径。在由致病性原生动物 spp. 和 引起的感染过程中，对播散性或慢性感染的易感性和/或炎症性疾病的发展取决于巨噬细胞介导的保护性免疫与抗炎反应之间的平衡。在此，我们将讨论利用巨噬细胞向极促炎的M1或促感染的M2表型转变的策略，以预防播散性和慢性感染的发生，或缓和寄生虫驱动的炎症反应。通过药理学方法、促M1细胞因子之间的协同作用以及针对促M2巨噬细胞功能（如胞葬作用），已在原生动物感染的实验模型中测试了巨噬细胞表型的免疫调节。我们将探讨旨在使巨噬细胞激活重定向至M1和M2表型的策略背后的细胞和分子机制，以及挑战和未解决的问题。
