Malaria parasite infection compromises control of concurrent systemic non-typhoidal Salmonella infection via IL-10-mediated alteration of myeloid cell function.
Malaria parasite infection compromises control of concurrent systemic non-typhoidal Salmonella infection via IL-10-mediated alteration of myeloid cell function.
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DOI：
10.1371/journal.ppat.1004049
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发表时间：
2014-05
期刊：
影响因子：
6.7
通讯作者：
Tsolis RM
中科院分区：
文献类型：
--
作者：
Lokken KL;Mooney JP;Butler BP;Xavier MN;Chau JY;Schaltenberg N;Begum RH;Müller W;Luckhart S;Tsolis RM
非伤寒沙门氏菌血清型（NTS）会在免疫功能正常的个体中引起自限性胃肠炎，而患有严重恶性疟原虫疟疾的儿童可能会出现危及生命的传播性感染。这种合并感染是撒哈拉以南非洲儿童死亡的主要原因。然而，疟疾导致NTS菌血症风险增加的机制尚不完全清楚。在这里，我们报告说，在小鼠共感染模型中，疟原虫感染减弱了对NTS的炎症反应，导致炎症病理减少和全身细菌定植增加。NTS诱导的炎症反应的钝化需要由寄生虫诱导IL-10。在没有疟原虫感染的情况下，施用重组IL-10连同诱导贫血对全身细菌定殖具有累加效应。条件性缺乏髓系细胞IL-10产生或髓系细胞IL-10受体表达的小鼠能够更好地控制全身沙门氏菌感染，表明吞噬细胞既是疟原虫诱导的IL-10的生产者，也是其靶点。因此，在对疟疾的免疫应答期间产生的IL-10通过抑制骨髓细胞（最可能是巨噬细胞）控制细菌感染的能力而增加对播散性NTS感染的易感性。非伤寒沙门氏菌血清型（NTS）最常引起自限性肠炎。然而，在撒哈拉以南非洲，NTS是危及生命的血流感染的最常见原因之一。患有这些血液感染的个体通常有潜在的疾病，如成人的艾滋病毒或儿童的疟疾。我们使用小鼠模型来研究为什么疟疾使儿童易患侵入性NTS感染。我们的研究结果表明，疟疾寄生虫通过细胞因子IL-10诱导的抗炎反应促进了从肠道传播到身体其他器官的细菌的生长。这种反应是有益的，因为它可以防止疟疾死亡，但对吞噬细胞有不利影响，阻止它们控制从肠道传播到身体其他器官的细菌生长的能力。
Non-typhoidal Salmonella serotypes (NTS) cause a self-limited gastroenteritis in immunocompetent individuals, while children with severe Plasmodium falciparum malaria can develop a life-threatening disseminated infection. This co-infection is a major source of child mortality in sub-Saharan Africa. However, the mechanisms by which malaria contributes to increased risk of NTS bacteremia are incompletely understood. Here, we report that in a mouse co-infection model, malaria parasite infection blunts inflammatory responses to NTS, leading to decreased inflammatory pathology and increased systemic bacterial colonization. Blunting of NTS-induced inflammatory responses required induction of IL-10 by the parasites. In the absence of malaria parasite infection, administration of recombinant IL-10 together with induction of anemia had an additive effect on systemic bacterial colonization. Mice that were conditionally deficient for either myeloid cell IL-10 production or myeloid cell expression of IL-10 receptor were better able to control systemic Salmonella infection, suggesting that phagocytic cells are both producers and targets of malaria parasite-induced IL-10. Thus, IL-10 produced during the immune response to malaria increases susceptibility to disseminated NTS infection by suppressing the ability of myeloid cells, most likely macrophages, to control bacterial infection. Non-typhoidal Salmonella serotypes (NTS) most frequently cause diarrheal disease, which is self-limiting. However, in sub-Saharan Africa, NTS is one of the most common causes of life-threatening bloodstream infections. Individuals with these bloodstream infections frequently have an underlying condition such as HIV in adults or malaria in children. We used a mouse model to investigate why malaria predisposes children to invasive NTS infections. Our results implicate an anti-inflammatory response induced by malaria parasites via the cytokine IL-10 in promoting increased growth of bacteria that have disseminated from the intestine to other organs of the body. This response is beneficial in that it prevents death from malaria, but has an adverse effect on phagocytic cells, blocking their ability to control growth of bacteria that have disseminated from the intestine to other organs of the body.
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影响因子：
8.7
作者：
Broz P;Monack DM
通讯作者：
Monack DM
影响因子：
168.9
作者：
Feasey, Nicholas A.;Dougan, Gordon;Kingsley, Robert A.;Heyderman, Robert S.;Gordon, Melita A.
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影响因子：
3.1
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Langhorne, J
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3
作者：
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Förster, I
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3.1
作者：
FRIEDMAN, RL;MOON, RJ
通讯作者：
MOON, RJ