One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through heme-oxygenase I (HO-I)-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during both acute parasitemia and up to 2 months after clearance of Py infected red blood cells that was independent of HO-I and IL-10. Py-infected mice were also susceptible to Streptococcus pneumoniae (Sp) bacteremia, a common malaria-bacteria co-infection, with higher blood and spleen bacterial burdens and decreased survival compared to naïve mice. Mechanistically, impaired immunity to Sp was independent of HO-I, but was dependent on Py-induced IL-10. Splenic phagocytes from Py infected mice exhibit an impaired ability to restrict growth of intracellular Lm, and neutrophils from Py-infected mice produce less reactive oxygen species (ROS) in response to Lm or Sp. Analysis also identified a defect in a serum component in Py-infected mice that contributes to reduced production of ROS in response to Sp. Finally, treating naïve mice with Plasmodium-derived hemozoin containing naturally bound bioactive molecules, excluding DNA, impaired clearance of Lm. Collectively, we have demonstrated that Plasmodium infection impairs host immunity to diverse bacteria, including S. pneumoniae, through multiple effects on innate immunity, and that a parasite-specific factor (Hz+bound bioactive molecules) directly contributes to Plasmodium-induced suppression of antibacterial innate immunity.

疟疾的一种并发症是对侵入性细菌感染的易感性增加。疟原虫感染会损害宿主对非伤寒的免疫力沙门氏菌(NTS) 通过血红素加氧酶 I (HO-I) 诱导释放未成熟粒细胞和骨髓细胞衍生的 IL-10。然而，尚不清楚这些机制是否特定于 NTS。我们在这里展示，约氏疟原虫17XNL (Py) 感染的小鼠全身清除能力受损李斯特菌(Lm) 在急性寄生虫血症期间和在清除不依赖于 HO-I 和 IL-10 的 Py 感染的红细胞后长达 2 个月。Py 感染的小鼠也容易感染肺炎链球菌(Sp) 菌血症，一种常见的疟疾-细菌共感染，与幼稚小鼠相比，血液和脾脏细菌负荷较高，存活率降低。从机制上讲，对 Sp 的免疫力受损与 HO-I 无关，但依赖于 Py 诱导的 IL-10。来自 Py 感染小鼠的脾吞噬细胞表现出限制细胞内 Lm 生长的能力受损，来自 Py 感染小鼠的中性粒细胞响应 Lm 或 Sp 产生较少的活性氧 (ROS)。分析还发现了感染 Py 的小鼠血清成分中的缺陷，该缺陷导致响应于 Sp。最后，用疟原虫含有天然结合的生物活性分子（不包括 DNA）的衍生 hemozoin 会损害 Lm 的清除。总的来说，我们已经证明疟原虫感染会损害宿主对多种细菌的免疫力，包括肺炎链球菌，通过对先天免疫的多重影响，以及寄生虫特异性因子（Hz+结合的生物活性分子）直接有助于疟原虫- 诱导抑制抗菌先天免疫。