Background: Pneumonia and diarrhea are among the leading causes of death worldwide, and epidemiological studies have demonstrated that diarrhea is associated with an increased risk of subsequent pneumonia. Our aim was to determine the impact of intestinal infection on innate immune responses in the lung. Methods: Using a mouse model of intestinal infection by Salmonella enterica serovar Typhimurium (S. Typhimurium (ST)), we investigated how infection in the gut compartment can modulate immunity in the lungs and impact susceptibility to bacterial (Klebsiella pneumoniae (KP)) challenge. Results: We found alterations in frequencies of innate immune cells in lungs of intestinally-infected mice compared to uninfected mice. On subsequent challenge with K. pneumoniae we found that mice with prior intestinal infection have higher lung bacterial burden and inflammation, increased neutrophil margination, and neutrophil extracellular traps (NETs), but lower overall numbers of neutrophils, compared to mice without prior intestinal infection. Total numbers of dendritic cells, innate-like T cells, and natural killer cells were not different between mice with and without prior intestinal infection. Conclusions: Together, these results suggest that intestinal infection impacts lung innate immune responses, most notably neutrophil characteristics, potentially resulting in increased susceptibility to secondary pneumonia.

中文翻译：

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肠感染会导致肺部对继发性呼吸道感染的先天免疫力受损。

背景：肺炎和腹泻是世界范围内死亡的主要原因，流行病学研究表明腹泻与随后发生肺炎的风险增加有关。我们的目的是确定肠感染对肺内固有免疫反应的影响。方法：使用鼠伤寒沙门氏菌（鼠伤寒沙门氏菌（ST））肠道感染的小鼠模型，我们调查了肠道隔间的感染如何调节肺部免疫力并影响对细菌（肺炎克雷伯菌）的易感性。结果：我们发现与未感染的小鼠相比，肠道感染的小鼠的肺中先天免疫细胞的频率发生了变化。随后与K挑战。我们发现，与没有肠道感染的小鼠相比，先前有肠道感染的小鼠的肺细菌负担和炎症更高，嗜中性粒细胞边缘化和嗜中性粒细胞胞外陷阱（NETs）增加，但嗜中性粒细胞总数却减少了。在有和没有肠道感染的小鼠之间，树突状细胞，先天样T细胞和自然杀伤细胞的总数没有差异。结论：这些结果共同表明，肠感染会影响肺固有免疫反应，尤其是嗜中性粒细胞特征，从而可能导致对继发性肺炎的易感性增加。在有和没有肠道感染的小鼠之间，树突状细胞，先天样T细胞和自然杀伤细胞的总数没有差异。结论：这些结果共同表明，肠感染会影响肺固有免疫反应，尤其是嗜中性粒细胞特征，从而可能导致对继发性肺炎的易感性增加。在有和没有肠道感染的小鼠之间，树突状细胞，先天样T细胞和自然杀伤细胞的总数没有差异。结论：这些结果共同表明，肠感染会影响肺固有免疫反应，尤其是嗜中性粒细胞特征，从而可能导致对继发性肺炎的易感性增加。