Mast cells and histamine alter intestinal permeability during malaria parasite infection.
Mast cells and histamine alter intestinal permeability during malaria parasite infection.
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DOI：
10.1016/j.imbio.2015.11.003
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发表时间：
2016-03
期刊：
影响因子：
2.8
通讯作者：
Luckhart S
中科院分区：
文献类型：
--
作者：
Potts RA;Tiffany CM;Pakpour N;Lokken KL;Tiffany CR;Cheung K;Tsolis RM;Luckhart S
疟疾和非伤寒沙门氏菌血清型（NTS）的合并感染可表现为危及生命的菌血症，与健康个体的自解NTS腹泻相反。在我们之前的疟疾/NTS合并感染小鼠模型中，我们发现肠道肥大细胞增多、回肠和血浆组胺水平增加与肠道通透性增加和细菌易位暂时相关。在这里，我们报告了肠道肥大细胞增多症和血浆组胺升高也与恶性疟疾动物模型中的疟疾有关，这表明这种生物学在更广泛的宿主分布。为了支持这种表型的肥大细胞功能，在肥大细胞缺陷小鼠中，疟疾/NTS联合感染与肠道通透性降低和菌血症相关。此外，抗组胺治疗减少了疟疾小鼠的细菌易位和肠道通透性，这表明肥大细胞源性组胺在疟疾/NTS合并感染期间对胃肠道病理和细菌血症的风险增加有贡献。
Co-infections with malaria and non-typhoidal Salmonella serotypes (NTS) can present as life-threatening bacteremia, in contrast to self-resolving NTS diarrhea in healthy individuals. In previous work with our mouse model of malaria/NTS co-infection, we showed increased gut mastocytosis and increased ileal and plasma histamine levels that were temporally associated with increased gut permeability and bacterial translocation. Here, we report that gut mastocytosis and elevated plasma histamine are also associated with malaria in an animal model of falciparum malaria, suggesting a broader host distribution of this biology. In support of mast cell function in this phenotype, malaria/NTS co-infection in mast cell-deficient mice was associated with a reduction in gut permeability and bacteremia. Further, antihistamine treatment reduced bacterial translocation and gut permeability in mice with malaria, suggesting a contribution of mast cell-derived histamine to GI pathology and enhanced risk of bacteremia during malaria/NTS co-infection.