卵巢激素影响金黄色葡萄球菌感染的免疫反应。

Ovarian hormones influence immune response to Staphylococcus aureus infection.

机构信息

Universidade Federal da Bahia, Instituto Multidisciplinar em Saúde, BA, Brazil.

Universidade Federal da Bahia, Instituto Multidisciplinar em Saúde, BA, Brazil; Universidade Estadual de Santa Cruz, Bahia, BA, Brazil.

出版信息

Braz J Infect Dis. 2020 Nov-Dec;24(6):534-544. doi: 10.1016/j.bjid.2020.10.004. Epub 2020 Nov 10.

DOI:10.1016/j.bjid.2020.10.004

PMID:33186580

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9392132/

Abstract

OBJECTIVE

Staphylococcus aureus infections remain associated with considerable morbidity and mortality in both hospitals and the community. There is little information regarding the role of ovarian hormones in infections caused by S. aureus. The aim of this study was to evaluate the effects of ovariectomy in the immune response induced by S. aureus.

METHODS

Female mice BALB/c were ovariectomized (OVX) to significantly reduce the level of ovarian hormones. We also used sham-operated animals. The mice were inoculated intraperitoneally with S. aureus. Blood samples were collected for leukocyte count and bacterial quantification. The uterus and spleen were removed and weighed to calculate the uterine and splenic indexes. Lungs were removed and fractionated for immunohistochemical analysis for macrophage detection (anti-CD68) and relative gene expression of IL-6, IL-1β and TNF-α by RT-PCR.

RESULTS

Ovariectomy enlarged spleen size and generally increased circulating lymphocytes. OVX females experienced a continuation of the initial reduction of lymphocytes and a monocyte and neutrophil late response compared to shams (p≥0.05). Moreover, OVX females showed neutropenia after 168h of infection (p≥0.05). Macrophage response in the lungs were less pronounced in OVX females in the initial hours of infection (p≥0.01). OVX females showed a higher relative gene expression of IL-1β, IL-6 and TNF-α in the lung at the beginning of the infection compared to sham females (p≥0.01). Among the uninfected females, the OVX control females showed a higher expression of IL-6 in the lung compared to the sham control females (p≥0.05). In this model, the lack of ovarian hormones caused a minor increase in circulating leukocytes during the initial stage of infection by S. aureus and increased pulmonary gene expression of IL-1β, IL-6, and TNF-α. Ovariectomy alone enlarged the spleen and increased circulating lymphocytes. Ovarian hormones acted as immunoprotectors against S. aureus infection.

摘要

目的

金黄色葡萄球菌感染在医院和社区中仍然与相当高的发病率和死亡率相关。关于卵巢激素在金黄色葡萄球菌引起的感染中的作用，信息很少。本研究旨在评估卵巢切除术对金黄色葡萄球菌诱导的免疫反应的影响。

方法

雌性 BALB/c 小鼠被卵巢切除术（OVX）以显著降低卵巢激素水平。我们还使用了假手术动物。小鼠被腹腔内接种金黄色葡萄球菌。采集血液样本进行白细胞计数和细菌定量。切除子宫和脾脏并称重，以计算子宫和脾脏指数。取出肺并进行免疫组织化学分析，以检测巨噬细胞（抗 CD68）和 RT-PCR 相对基因表达的 IL-6、IL-1β 和 TNF-α。

结果

卵巢切除术使脾脏增大，并普遍增加循环淋巴细胞。与假手术相比，OVX 雌性经历了初始淋巴细胞减少的持续时间和晚期单核细胞和中性粒细胞反应（p≥0.05）。此外，OVX 雌性在感染 168 小时后出现中性粒细胞减少（p≥0.05）。在感染的最初几个小时，OVX 雌性肺部的巨噬细胞反应不那么明显（p≥0.01）。与 sham 雌性相比，OVX 雌性在感染开始时肺部的 IL-1β、IL-6 和 TNF-α 相对基因表达更高（p≥0.01）。在未感染的雌性中，与 sham 对照组雌性相比，OVX 对照组雌性的肺部 IL-6 表达更高（p≥0.05）。在该模型中，缺乏卵巢激素在金黄色葡萄球菌感染的初始阶段导致循环白细胞轻度增加，并增加了肺部的 IL-1β、IL-6 和 TNF-α 基因表达。单独的卵巢切除术使脾脏增大并增加了循环淋巴细胞。卵巢激素作为金黄色葡萄球菌感染的免疫保护剂。