Cathelicidins are a class of antimicrobial peptide, and the murine cathelicidin-related antimicrobial peptide (mCRAMP) has been demonstrated in vitro to impair Salmonella enterica serovar Typhimurium proliferation. However, the impact of mCRAMP on host responses and the microbiota following S. Typhimurium infection has not been determined. In this study mCRAMP−/− and mCRAMP+/+ mice (± streptomycin) were orally inoculated with S. enterica serovar Typhimurium DT104 (SA +), and impacts on the host and enteric bacterial communities were temporally evaluated. Higher densities of the pathogen were observed in cecal digesta and associated with mucosa in SA+/mCRAMP−/− mice that were pretreated (ST+) and not pretreated (ST−) with streptomycin at 24 h post-inoculation (hpi). Both SA+/ST+/mCRAMP−/− and SA+/ST−/mCRAMP−/− mice were more susceptible to infection exhibiting greater histopathologic changes (e.g. epithelial injury, leukocyte infiltration, goblet cell loss) at 48 hpi. Correspondingly, immune responses in SA+/ST+/mCRAMP–/− and SA+/ST−/mCRAMP–/− mice were affected (e.g. Ifnγ, Kc, Inos, Il1β, RegIIIγ). Systemic dissemination of the pathogen was characterized by metabolomics, and the liver metabolome was affected to a greater degree in SA+/ST+/mCRAMP–/− and SA+/ST−/mCRAMP–/− mice (e.g. taurine, cadaverine). Treatment-specific changes to the structure of the enteric microbiota were associated with infection and mCRAMP deficiency, with a higher abundance of Enterobacteriaceae and Veillonellaceae observed in infected null mice. The microbiota of mice that were administered the antibiotic and infected with Salmonella was dominated by Proteobacteria. The study findings showed that the absence of mCRAMP modulated both host responses and the enteric microbiota enhancing local and systemic infection by Salmonella Typhimurium.

中文翻译：

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缺少小鼠导管素相关抗菌肽会影响宿主反应，增强肠炎沙门氏菌血清鼠伤寒感染

速激肽是一类抗菌肽，并且已经证明鼠类Cathelicidin相关的抗菌肽（mCRAMP）会损害肠炎沙门氏菌血清鼠伤寒病毒的增殖。但是，尚未确定mCRAMP对鼠伤寒沙门氏菌感染后宿主反应和微生物群的影响。在这项研究中，将mCRAMP-/-和mCRAMP + / +小鼠（±链霉素）口服接种肠炎链球菌血清鼠伤寒DT104（SA +），并临时评估其对宿主和肠道细菌群落的影响。在盲肠消化道中观察到病原体的密度更高，并且在接种后24 h（hpi）进行链霉素预处理（ST +）和未进行预处理（ST-）的SA + / mCRAMP-/-小鼠中，其黏膜相关。SA + / ST + / mCRAMP-/-和SA + / ST- / mCRAMP-/-小鼠在48 hpi时更容易受到感染，表现出更大的组织病理学变化（例如上皮损伤，白细胞浸润，杯状细胞丢失）。相应地，SA + / ST + / mCRAMP-/-和SA + / ST- / mCRAMP-/-小鼠的免疫反应受到影响（例如，Ifnγ，Kc，Inos，Il1β，RegIIIγ）。代谢组学表征了病原体的全身传播，SA + / ST + / mCRAMP-/-和SA + / ST- / mCRAMP-/-小鼠（例如牛磺酸，尸胺）对肝脏代谢组的影响更大。肠道菌群结构的治疗特异性变化与感染和mCRAMP缺乏症有关，在感染的无效小鼠中观察到肠杆菌科和Veillonellaceae的丰度更高。注射抗生素并被沙门氏菌感染的小鼠的微生物群被变形杆菌所控制。研究发现表明，缺乏mCRAMP既可以调节宿主反应，也可以增强肠道微生物群，从而增强鼠伤寒沙门氏菌的局部和全身感染。