Advanced Environmental Research Institute, Department of Biological Sciences, University of North Texas, EESAT - 215, 1704 W. Mulberry, Denton, TX, 76201, USA.
Part Fibre Toxicol. 2024 Sep 29;21(1):40. doi: 10.1186/s12989-024-00601-w.
Both exposure to air pollutants and obesity are associated with increased incidence and severity of COVID-19 infection; however, the mechanistic pathways involved are not well-characterized. After being primed by the transmembrane protease serine 2 (TMPRSS2) or furin protease, SARS-CoV-2 uses the angiotensin-converting enzyme (ACE)-2 receptor to enter respiratory epithelial cells. The androgen receptor (AR) is known to regulate both TMPRSS2 and ACE2 expression, and neuropilin-1 (NRP1) is a proposed coreceptor for SARS-CoV-2; thus, altered expression of these factors may promote susceptibility to infection. As such, this study investigated the hypothesis that inhalational exposure to traffic-generated particulate matter (diesel exhaust particulate; DEP) increases the expression of those pathways that mediate SARS-CoV-2 infection and susceptibility, which is exacerbated by the consumption of a high-fat (HF) diet.
Four- to six-week-old male C57BL/6 mice fed either regular chow or a HF diet (HF, 45% kcal from fat) were randomly assigned to be exposed via oropharyngeal aspiration to 35 µg DEP suspended in 35 µl 0.9% sterile saline or sterile saline only (control) twice a week for 30 days. Furthermore, as previous studies have shown that probiotic treatment can protect against exposure-related inflammatory outcomes in the lungs, a subset of study animals fed a HF diet were concurrently treated with 0.3 g/day Winclove Ecologic Barrier probiotics in their drinking water throughout the study.
Our results revealed that the expression of ACE2 protein increased with DEP exposure and that TMPRSS2, AR, NRP1, and furin protein expression increased with DEP exposure in conjunction with a HF diet. These DEP ± HF diet-mediated increases in expression were mitigated with probiotic treatment.
These findings suggest that inhalational exposure to air pollutants in conjunction with the consumption of a HF diet contributes to a more susceptible lung environment to SARS-CoV-2 infection and that probiotic treatment could be beneficial as a preventative measure.
暴露于空气污染物和肥胖都会增加 COVID-19 感染的发生率和严重程度；然而，其涉及的机制途径尚未得到很好的描述。SARS-CoV-2 在被跨膜丝氨酸蛋白酶 2（TMPRSS2）或弗林蛋白酶激活后，利用血管紧张素转换酶（ACE）-2 受体进入呼吸道上皮细胞。已知雄激素受体（AR）调节 TMPRSS2 和 ACE2 的表达，神经纤毛蛋白-1（NRP1）是 SARS-CoV-2 的一个拟议核心受体；因此，这些因素的表达改变可能会促进感染易感性。因此，本研究假设吸入交通产生的颗粒物（柴油废气颗粒；DEP）会增加介导 SARS-CoV-2 感染和易感性的途径的表达，而高脂肪（HF）饮食会加剧这种情况。
4 至 6 周龄雄性 C57BL/6 小鼠分别用普通饲料或高脂肪（HF，脂肪热量的 45%）喂养，随机分为经口吸入法暴露于 35µg 悬浮在 35µl 0.9%无菌盐水中的 DEP 或仅无菌盐水（对照），每周两次，共 30 天。此外，正如先前的研究表明，益生菌治疗可以保护肺部免受与暴露相关的炎症后果，因此，一部分用 HF 饮食喂养的研究动物在整个研究过程中同时用 0.3g/天的 Winclove Ecologic Barrier 益生菌治疗。
我们的结果表明，ACE2 蛋白的表达随着 DEP 的暴露而增加，而 TMPRSS2、AR、NRP1 和弗林蛋白酶蛋白的表达随着 DEP 暴露以及 HF 饮食的增加而增加。这些 DEP±HF 饮食介导的表达增加被益生菌治疗减轻。
这些发现表明，空气污染物的吸入暴露与高脂肪饮食的摄入会导致对 SARS-CoV-2 感染更易感的肺部环境，而益生菌治疗可能作为一种预防措施有益。
