Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Millennium Institute on Immunology and Immunotherapy, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, Chile.
Front Immunol. 2024 Feb 2;15:1330209. doi: 10.3389/fimmu.2024.1330209. eCollection 2024.
Respiratory infections are one of the leading causes of morbidity and mortality worldwide, mainly in children, immunocompromised people, and the elderly. Several respiratory viruses can induce intestinal inflammation and alterations in intestinal microbiota composition. Human metapneumovirus (HMPV) is one of the major respiratory viruses contributing to infant mortality in children under 5 years of age worldwide, and the effect of this infection at the gut level has not been studied.
Here, we evaluated the distal effects of HMPV infection on intestinal microbiota and inflammation in a murine model, analyzing several post-infection times (days 1, 3, and 5). Six to eight-week-old C57BL/6 mice were infected intranasally with HMPV, and mice inoculated with a non-infectious supernatant (Mock) were used as a control group.
We did not detect HMPV viral load in the intestine, but we observed significant changes in the transcription of IFN-γ in the colon, analyzed by qPCR, at day 1 post-infection as compared to the control group. Furthermore, we analyzed the frequencies of different innate and adaptive immune cells in the colonic lamina propria, using flow cytometry. The frequency of monocyte populations was altered in the colon of HMPV -infected mice at days 1 and 3, with no significant difference from control mice at day 5 post-infection. Moreover, colonic CD8 T cells and memory precursor effector CD8 T cells were significantly increased in HMPV-infected mice at day 5, suggesting that HMPV may also alter intestinal adaptive immunity. Additionally, we did not find alterations in antimicrobial peptide expression, the frequency of colonic IgA plasma cells, and levels of fecal IgA. Some minor alterations in the fecal microbiota composition of HMPV -infected mice were detected using 16s rRNA sequencing. However, no significant differences were found in β-diversity and relative abundance at the genus level.
To our knowledge, this is the first report describing the alterations in intestinal immunity following respiratory infection with HMPV infection. These effects do not seem to be mediated by direct viral infection in the intestinal tract. Our results indicate that HMPV can affect colonic innate and adaptive immunity but does not significantly alter the microbiota composition, and further research is required to understand the mechanisms inducing these distal effects in the intestine.
呼吸道感染是全球发病率和死亡率的主要原因之一，主要发生在儿童、免疫功能低下者和老年人中。几种呼吸道病毒可诱导肠道炎症和肠道微生物群落组成的改变。人类偏肺病毒（HMPV）是导致全球 5 岁以下儿童死亡的主要呼吸道病毒之一，但这种感染对肠道的影响尚未得到研究。
在这里，我们在小鼠模型中评估了 HMPV 感染对肠道微生物群和炎症的远端影响，分析了感染后的多个时间点（第 1、3 和 5 天）。用 HMPV 鼻腔感染 6 至 8 周龄 C57BL/6 小鼠，用非感染性上清液（Mock）感染的小鼠作为对照组。
我们未在肠道中检测到 HMPV 病毒载量，但通过 qPCR 分析，与对照组相比，感染后第 1 天结肠中 IFN-γ 的转录显著改变。此外，我们使用流式细胞术分析了结肠固有层中不同固有和适应性免疫细胞的频率。感染后第 1 和第 3 天，HMPV 感染小鼠的单核细胞群体在结肠中的频率发生改变，但与感染后第 5 天的对照小鼠相比没有差异。此外，在感染后第 5 天，HMPV 感染小鼠的结肠 CD8 T 细胞和记忆前体效应 CD8 T 细胞显著增加，这表明 HMPV 也可能改变肠道适应性免疫。此外，我们没有发现抗菌肽表达、结肠 IgA 浆细胞的频率和粪便 IgA 水平的改变。通过 16s rRNA 测序检测到 HMPV 感染小鼠粪便微生物群落组成的一些微小改变。然而，在β多样性和属水平的相对丰度方面没有发现显著差异。
据我们所知，这是第一个描述呼吸道感染后 HMPV 感染引起的肠道免疫改变的报告。这些影响似乎不是由肠道内病毒的直接感染引起的。我们的结果表明，HMPV 可以影响结肠固有和适应性免疫，但不会显著改变微生物群落组成，需要进一步研究以了解诱导这些肠道远端效应的机制。
