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Alongside their well-established role in hemostasis, platelets are key modulators of immune cell function. This is particularly the case for macrophages, as platelets can either promote or dampen macrophage activation in a context-specific manner. Whilst the role of platelets in modulating classical (M1) macrophage activation following bacterial challenge is relatively well understood, whether platelets control other macrophage responses is less clear. We investigated the role of platelets in type 2 inflammation using a mouse model of chronic schistosomiasis. Schistosome infection caused thrombocytopenia which was not fully reversed after drug-induced parasite death. Reduced platelet levels in infection were coincident with lower levels of systemic TPO and extensive liver damage caused by parasite eggs. Infection also reduced the ploidy and size (but not number) of bone marrow megakaryocytes, which was associated with reduced platelet output. We show schistosome infection accelerated platelet clearance and promoted the formation of platelet-leukocyte aggregates. This was particularly the case for liver macrophages and monocytes. Phenotypic analysis shows that platelet-associated liver macrophages had a distinct activation phenotype that included elevated expression of the alternative (M2) activation marker RELMα. Despite this, in vitro studies indicated that platelets do not directly promote macrophage alternative activation. Similarly, whilst in vivo pharmacological treatment with a TPO mimetic enhanced platelet numbers and platelet-leukocyte aggregates, this did not alter macrophage phenotype. Conversely, antibody-mediated depletion of platelets or use of platelet-deficient mice both led to extensive bleeding following infection which impacted host survival. Together, these data indicate that whilst platelets are essential to prevent excessive disease pathology in schistosomiasis, they have a more nuanced role in myeloid cell activation and type 2 immune responses.

血小板（platelets）在止血（hemostasis）中已被广泛证实具有关键作用，同时亦是调控免疫细胞功能的核心因子，这一作用在巨噬细胞（macrophages）中尤为突出——血小板可依情境不同，分别促进或抑制巨噬细胞的活化。目前学界对血小板在细菌攻击后调控经典（M1型）巨噬细胞活化的机制已有较充分的认识，但血小板是否能调控其他类型的巨噬细胞应答仍尚不明确。本研究借助慢性血吸虫病小鼠模型，探究了血小板在2型炎症中的调控作用。研究发现，血吸虫感染可引发血小板减少症（thrombocytopenia），且该症状在药物诱导寄生虫死亡后并未完全逆转。感染状态下血小板水平的降低，与全身性血小板生成素（TPO）水平下降以及寄生虫虫卵诱发的广泛肝损伤呈现同步变化。此外，感染还会降低骨髓巨核细胞（bone marrow megakaryocytes）的倍性与体积（但不影响其数量），这与血小板生成量的减少密切相关。本研究证实，血吸虫感染会加速血小板的清除，并促进血小板-白细胞聚集体（platelet-leukocyte aggregates）的形成，这一现象在肝脏巨噬细胞与单核细胞中尤为显著。表型分析显示，与血小板结合的肝脏巨噬细胞具有独特的活化表型，其替代性（M2型）活化标志物RELMα的表达水平显著升高。尽管如此，体外（in vitro）实验表明血小板并不会直接促进巨噬细胞的替代性活化。类似地，尽管体内（in vivo）采用TPO模拟剂（TPO mimetic）进行药物干预可提升血小板数量与血小板-白细胞聚集体水平，但并未改变巨噬细胞的表型。反之，通过抗体介导耗竭血小板或使用血小板缺陷小鼠（platelet-deficient mice），均会导致感染后出现严重出血，进而影响宿主的存活率。综上，本研究数据表明，尽管血小板对于防止血吸虫病出现过度病理损伤至关重要，但它们在髓系细胞活化与2型免疫应答中发挥的作用更为复杂精细。