Malaria impairs resistance to Salmonella through heme- and heme oxygenase-dependent dysfunctional granulocyte mobilization.
Malaria impairs resistance to Salmonella through heme- and heme oxygenase-dependent dysfunctional granulocyte mobilization.
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在撒哈拉以南非洲，侵袭性非伤寒沙门氏菌（NTS）是恶性疟原虫感染的常见且往往致命的并发症。血红素加氧酶-1（HO-1）的诱导介导了疟疾溶血过程中对血红素细胞毒性作用的耐受性，但可能通过限制杀菌活性氧的产生而削弱对NTS的抵抗力。结果表明，约氏疟原虫17 XNL（Py 17 XNL）和S.鼠伤寒引起急性、致命的菌血症，细菌负荷增加;苯肼溶血或氯化高铁血红素给药可重现这些特征。S.鼠伤寒杆菌主要分布于粒细胞中。Py 17 XNL，苯肼和氯化血红素引起过早动员粒细胞从骨髓中的氧化爆发的定量缺陷。用锡原卟啉抑制HO，可消除对S.溶血致鼠伤寒沙门氏菌。因此，对一种感染（疟疾）的耐受机制削弱了对另一种感染（NTS）的抵抗力。此外，HO抑制剂可能是用于NTS感染的溶血背景下的有效治疗。
In sub-Saharan Africa, invasive non-Typhoid Salmonella (NTS) is a common and often fatal complication of Plasmodium falciparum infection. Induction of heme oxygenase-1 (HO-1) mediates tolerance to the cytotoxic effects of heme during malarial hemolysis but might impair resistance to NTS by limiting production of bactericidal reactive oxygen species. We show that co-infection of mice with Plasmodium yoelii 17XNL (Py17XNL) and S. typhimurium causes acute, fatal bacteremia with increased bacterial load; features reproduced by phenylhydrazine hemolysis or hemin administration. S. typhimurium localized predominantly in granulocytes. Py17XNL, phenylhydrazine and hemin caused premature mobilization of granulocytes from bone marrow with a quantitative defect in the oxidative burst. Inhibition of HO by tin protoporphyrin abrogated the impairment of resistance to S. typhimurium by hemolysis. Thus a mechanism of tolerance to one infection, malaria, impairs resistance to another, NTS. Furthermore, HO inhibitors may be useful adjunctive therapy for NTS infection in the context of hemolysis.
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影响因子：
15.3
作者：
Mastroeni, P;Vazquez-Torres, A;Fang, F C;Xu, Y;Khan, S;Hormaeche, C E;Dougan, G
通讯作者：
Dougan, G
影响因子：
64.5
作者：
Ferreira, Ana;Marguti, Ivo;Soares, Miguel P.
通讯作者：
Soares, Miguel P.
影响因子：
15.9
作者：
Belcher, JD;Mahaseth, H;Vercellotti, GM
通讯作者：
Vercellotti, GM
DOI：
10.3181/00379727-120-30661
发表时间：
1965-01-01
影响因子：
--
作者：
KAYE, D;MERSELIS, JG;HOOK, EW
通讯作者：
HOOK, EW
影响因子：
3.1
作者：
MURPHY, JR
通讯作者：
MURPHY, JR