Malaria-induced bacteremia as a consequence of multiple parasite survival strategies.
Malaria-induced bacteremia as a consequence of multiple parasite survival strategies.
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DOI：
10.1016/j.crmicr.2021.100036
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发表时间：
2021-12
影响因子：
--
通讯作者：
Luckhart S
中科院分区：
文献类型：
--
作者：
Donnelly E;de Water JV;Luckhart S
疟疾寄生虫操纵哺乳动物的免疫反应，以促进生存。寄生虫通过诱导Th 2型应答来抑制细胞毒性/抗寄生虫应答。除了促进存活外，Th 2应答还改变了对蚊子的传播。伴随菌血症与疟疾感染可能是这种操作的产物。在全球范围内，疟疾仍然是一个巨大的公共卫生负担，伴随着寄生虫引起的胃肠道（GI）屏障损害，导致成人和儿童的菌血症相关的发病率和死亡率。受感染的红细胞隔离在胃肠道微血管系统中并可能阻塞胃肠道微血管系统，最终导致通常作为肠道细菌易位物理屏障的紧密和粘附连接的破坏。在疟疾期间肥大细胞（MC）活化和移位至GI加剧了对物理屏障的损害，并通过释放改变宿主对逃逸的肠道细菌的反应的酶和因子来削弱免疫屏障。在这种情况下，活化的MC释放Th 2细胞因子，促进平衡的Th 1/Th 2反应，增加局部和全身过敏性炎症，同时保护宿主免受压倒性Th 1介导的免疫病理学。除了哺乳动物宿主之外，最近在实验室和现场的研究都揭示了Th 2偏斜宿主反应与寄生虫成功传播到蚊子之间的关联，这是对哺乳动物宿主的寄生虫操纵的唤起。总的来说，这些观察结果表明，疟疾引起的菌血症可能是，在某种程度上，一个意想不到的后果Th 2移位主机响应，促进寄生虫的生存和传播。这项工作的未来方向包括确定菌血症发展之前的因素和机制，这将使生物标志物的开发能够简化诊断，确定治疗靶点以改善患者的预后，并更好地了解临床干预措施对传播阻断策略的影响。
Malaria parasites manipulate the mammalian immune response to facilitate survival. Parasites dampen cytotoxic/antiparasitic responses by inducing Th2-type responses. In addition to promoting survival, Th2 responses alter transmission to mosquitoes. Concomitant bacteremia with malaria infection may be a product of this manipulation. Globally, malaria continues to be an enormous public health burden, with concomitant parasite-induced damage to the gastrointestinal (GI) barrier resulting in bacteremia-associated morbidity and mortality in both adults and children. Infected red blood cells sequester in and can occlude the GI microvasculature, ultimately leading to disruption of the tight and adherens junctions that would normally serve as a physical barrier to translocating enteric bacteria. Mast cell (MC) activation and translocation to the GI during malaria intensifies damage to the physical barrier and weakens the immunological barrier through the release of enzymes and factors that alter the host response to escaped enteric bacteria. In this context, activated MCs release Th2 cytokines, promoting a balanced Th1/Th2 response that increases local and systemic allergic inflammation while protecting the host from overwhelming Th1-mediated immunopathology. Beyond the mammalian host, recent studies in both the lab and field have revealed an association between a Th2-skewed host response and success of parasite transmission to mosquitoes, biology that is evocative of parasite manipulation of the mammalian host. Collectively, these observations suggest that malaria-induced bacteremia may be, in part, an unintended consequence of a Th2-shifted host response that promotes parasite survival and transmission. Future directions of this work include defining the factors and mechanisms that precede the development of bacteremia, which will enable the development of biomarkers to simplify diagnostics, the identification of therapeutic targets to improve patient outcomes and better understanding of the consequences of clinical interventions to transmission blocking strategies.
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影响因子：
2.4
作者：
Bischoff SC;Barbara G;Buurman W;Ockhuizen T;Schulzke JD;Serino M;Tilg H;Watson A;Wells JM
通讯作者：
Wells JM
DOI：
10.4049/jimmunol.1301389
发表时间：
2013-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Colpitts SL;Stonier SW;Stoklasek TA;Root SH;Aguila HL;Schluns KS;Lefrançois L
通讯作者：
Lefrançois L
影响因子：
6
作者：
Al-Sadi, Rana;Guo, Shuhong;Ma, Thomas Y.
通讯作者：
Ma, Thomas Y.
DOI：
10.1016/s0035-9203(99)90024-x
发表时间：
1999-05-01
影响因子：
2.2
作者：
Berkley, J;Mwarumba, S;Marsh, K
通讯作者：
Marsh, K
影响因子：
12.4
作者：
BURY, TB;CORHAY, JL;RADERMECKER, MF
通讯作者：
RADERMECKER, MF