Departments of *Medicine; †Laboratory Medicine and Pathobiology; ‡Immunology, University of Toronto, Toronto, Ontario, Canada; §Department of Medical Microbiology University of Nairobi, Nairobi, Kenya; and ‖Sandra A. Rotman Laboratories, Sandra Rotman Centre for Global Health, Tropical Disease Unit, Toronto General Hospital, University Health Network.
J Acquir Immune Defic Syndr. 2014 Apr 15;65(5):517-25. doi: 10.1097/QAI.0000000000000056.
To evaluate if systemic murine malarial infection enhances HIV susceptibility through parasite-induced mucosal immune alterations at sites of HIV sexual exposure.
Malaria and HIV have a high degree of geographical overlap and interact substantially within coinfected individuals. We used a murine model to test the hypothesis that malaria might also enhance HIV susceptibility at mucosal sites of HIV sexual exposure.
Female C57/BL6 mice were infected with Plasmodium chabaudi malaria using a standardized protocol. Blood, gastrointestinal tissues, upper and lower genital tract tissues, and iliac lymph nodes were sampled 10 days postinfection, and the expression of putative HIV susceptibility and immune activation markers on T cells was assessed by flow cytometry.
P. chabaudi malaria increased expression of mucosal homing integrin α4β7 on blood CD4 and CD8 T cells, and these α4β7 T cells had significantly increased co-expression of both CCR5 and CD38. In addition, malaria increased expression of the HIV co-receptor CCR5 on CD4 T cells from the genital tract and gut mucosa as well as mucosal T-cell expression of the immune activation markers CD38, Major Histocompatibility Complex -II (MHC-II) and CD69.
Systemic murine malarial infection induced substantial upregulation of the mucosal homing integrin α4β7 in blood as well as gut and genital mucosal T-cell immune activation and HIV co-receptor expression. Human studies are required to confirm these murine findings and to examine whether malarial infection enhances the sexual acquisition of HIV.
评估系统性鼠疟感染是否通过寄生虫诱导的 HIV 性接触部位黏膜免疫改变增强 HIV 易感性。
疟疾和 HIV 在地理上高度重叠，在合并感染个体中存在实质性相互作用。我们使用一种鼠模型来检验这样一种假设，即疟疾也可能增强 HIV 性接触部位的 HIV 易感性。
采用标准化方案，用疟原虫 Plasmodium chabaudi 感染雌性 C57/BL6 小鼠。感染后 10 天，采集血液、胃肠道组织、上生殖道组织和下生殖道组织及髂淋巴结，采用流式细胞术评估 T 细胞上假定的 HIV 易感性和免疫激活标志物的表达。
P. chabaudi 疟疾增加了血液 CD4 和 CD8 T 细胞上黏膜归巢整合素 α4β7 的表达，这些 α4β7 T 细胞显著增加了 CCR5 和 CD38 的共表达。此外，疟疾增加了生殖道和肠道黏膜 CD4 T 细胞上 HIV 辅助受体 CCR5 的表达，以及黏膜 T 细胞上免疫激活标志物 CD38、主要组织相容性复合体-II（MHC-II）和 CD69 的表达。
系统性鼠疟感染诱导血液以及肠道和生殖道黏膜 T 细胞免疫激活和 HIV 辅助受体表达的黏膜归巢整合素 α4β7 大量上调。需要进行人类研究来证实这些鼠类发现，并研究疟疾感染是否增强了 HIV 的性传播。
