Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
PLoS One. 2018 Jun 1;13(6):e0198434. doi: 10.1371/journal.pone.0198434. eCollection 2018.
Polymeric immunoglobulin receptor (pIgR) transport of secretory immunoglobulin A (SIgA) to mucosal surfaces is thought to promote gut integrity and immunity to Salmonella enterica serovar Typhimurium (S. Typhimurium), an invasive pathogen in mice. To elucidate potential mechanisms, we assessed intestinal barrier function and both oral and systemic S. Typhimurium virulence in pIgR knockout (KO) and wildtype (WT) mice.
In uninfected animals, we harvested jejunal segments for Ussing chamber analyses of transepithelial resistance (TER); mesenteric lymph nodes (mLN) for bacterial culture; and serum and stool for IgA. Separately, we infected mice either orally or intravenously (IV) with S. Typhimurium to compare colonization, tissue dynamics, and inflammation between KOs and WTs.
Uninfected KOs displayed decreased TER and dramatically increased serum IgA and decreased fecal IgA vs. WT; however, KO mLNs yielded fewer bacterial counts. Remarkably, WTs challenged orally with S. Typhimurium exhibited increased splenomegaly, tissue colonization, and pro-inflammatory cytokines vs. pIgR KOs, which showed increased survival following either oral or IV infection.
Absence of pIgR compromises gut integrity but does not exacerbate bacterial translocation nor S. Typhimurium infection. These findings raise the possibility that immune adaptation to increased gut permeability and elevated serum IgA in the setting of SIgA deficiency provides compensatory protection against invasive gut pathogens.
多免疫球蛋白受体（pIgR）将分泌型免疫球蛋白 A（SIgA）转运到黏膜表面被认为可促进肠道完整性和对鼠伤寒沙门氏菌（S. Typhimurium）的免疫力，S. Typhimurium 是一种侵袭性病原体。为了阐明潜在的机制，我们评估了 pIgR 敲除（KO）和野生型（WT）小鼠的肠道屏障功能以及口服和全身 S. Typhimurium 毒力。
在未感染的动物中，我们采集空肠段进行 Ussing 室分析跨上皮电阻（TER）；肠系膜淋巴结（mLN）进行细菌培养；血清和粪便用于 IgA。分别用鼠伤寒沙门氏菌口服或静脉（IV）感染小鼠，比较 KO 和 WT 之间的定植、组织动态和炎症。
未感染的 KO 显示 TER 降低，血清 IgA 显著增加，粪便 IgA 降低，与 WT 相比；然而，KO 的 mLN 计数较少。值得注意的是，口服鼠伤寒沙门氏菌挑战的 WT 显示脾肿大、组织定植和促炎细胞因子增加，而 pIgR KO 则显示口服或 IV 感染后存活率增加。
pIgR 的缺失会损害肠道完整性，但不会加重细菌易位或 S. Typhimurium 感染。这些发现提出了一种可能性，即在 SIgA 缺乏的情况下，对肠道通透性增加和血清 IgA 升高的免疫适应提供了对侵袭性肠道病原体的补偿性保护。
