关键词: Ascaris Salmonella Coinfection Natural killer cells

Mesh : Animals Killer Cells, Natural / immunology metabolism Ascariasis / immunology veterinary parasitology Coinfection / immunology microbiology parasitology Swine Swine Diseases / parasitology immunology microbiology Salmonella Infections, Animal / immunology Salmonella typhimurium / immunology pathogenicity Ascaris suum / immunology Interferon-gamma / metabolism Perforin / metabolism Interleukin-12 / metabolism T-Box Domain Proteins / metabolism genetics Interleukin-18 / metabolism

来  源:   DOI:10.1038/s41598-024-64497-4   PDF(Pubmed)

Abstract:
Natural killer (NK) cells play a key role in defense against Salmonella infections during the early phase of infection. Our previous work showed that the excretory/secretory products of Ascaris suum repressed NK activity in vitro. Here, we asked if NK cell functionality was influenced in domestic pigs during coinfection with Ascaris and Salmonella enterica serotype Typhimurium. Ascaris coinfection completely abolished the IL-12 and IL-18 driven elevation of IFN-γ production seen in CD16 + CD8α + perforin + NK cells of Salmonella single-infected pigs. Furthermore, Ascaris coinfection prohibited the Salmonella-driven rise in NK perforin levels and CD107a surface expression. In line with impaired effector functions, NK cells from Ascaris-single and coinfected pigs displayed elevated expression of the inhibitory KLRA1 and NKG2A receptors genes, contrasting with the higher expression of the activating NKp46 and NKp30 receptors in NK cells during Salmonella single infection. These differences were accompanied by the highly significant upregulation of T-bet protein expression in NK cells from Ascaris-single and Ascaris/Salmonella coinfected pigs. Together, our data strongly indicate a profound repression of NK functionality by an Ascaris infection which may hinder infected individuals from adequately responding to a concurrent bacterial infection.
摘要:
自然杀伤(NK)细胞在感染早期对沙门氏菌感染的防御中起关键作用。我们先前的工作表明,A虫的排泄/分泌产物在体外抑制了NK活性。这里,我们询问家猪在与蛔虫和沙门氏菌血清型鼠伤寒合并感染期间,NK细胞功能是否受到影响。蛔虫共感染完全消除了沙门氏菌单感染猪的CD16CD8α穿孔素NK细胞中IL-12和IL-18驱动的IFN-γ产生升高。此外,蛔虫共感染阻止了沙门氏菌驱动的NK穿孔素水平和CD107a表面表达的升高。根据受损的效应器功能,单个和合并感染猪的NK细胞显示抑制性KLRA1和NKG2A受体基因的表达升高,与沙门氏菌单次感染期间NK细胞中激活的NKp46和NKp30受体的较高表达相反。这些差异伴随着A虫和A虫/沙门氏菌共感染的猪的NK细胞中T-bet蛋白表达的高度显著上调。一起,我们的数据强烈表明,蛔虫感染对NK功能的严重抑制,这可能会阻碍感染者对并发细菌感染的充分反应.
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