Department of Biological Sciences, California State University Los Angeles, Los Angeles, California, USA.
Infect Immun. 2012 Jan;80(1):266-75. doi: 10.1128/IAI.05638-11. Epub 2011 Oct 17.
Paneth cells residing at the base of the small intestinal crypts contribute to the mucosal intestinal first line defense by secreting granules filled with antimicrobial polypeptides including lysozyme. These cells derive from the columnar intestinal stem cell located at position 0 and the transit amplifying cell located at position +4 in the crypts. We have previously shown that Salmonella enterica serovar Typhimurium (ST), a leading cause of gastrointestinal infections in humans, effects an overall reduction of lysozyme in the small intestine. To extend this work, we examined small-intestinal tissue sections at various time points after ST infection to quantify and localize expression of lysozyme and assess Paneth cell abundance, apoptosis, and the expression of Paneth cell differentiation markers. In response to infection with ST, the intestinal Paneth cell-specific lysozyme content, the number of lysozyme-positive Paneth cells, and the number of granules per Paneth cell decreased. However, this was accompanied by increases in the total number of Paneth cells and the frequency of mitotic events in crypts, by increased staining for the proliferation marker PCNA, primarily at the crypt side walls where the transit amplifying cell resides and not at the crypt base, and by apoptotic events in villi. Furthermore, we found a time-dependent upregulation of first β-catenin, followed by EphB3, and lastly Sox9 in response to ST, which was not observed after infection with a Salmonella pathogenicity island 1 mutant deficient in type III secretion. Our data strongly suggest that, in response to ST infection, a Paneth cell differentiation program is initiated that leads to an expansion of the Paneth cell population and that the transit amplifying cell is likely the main progenitor responder. Infection-induced expansion of the Paneth cell population may represent an acute intestinal inflammatory response similar to neutrophilia in systemic infection.
位于小肠隐窝底部的潘氏细胞通过分泌充满抗菌多肽的颗粒（包括溶菌酶）来参与肠道黏膜的第一道防线。这些细胞来源于位于隐窝 0 位的柱状肠干细胞和位于隐窝+4 位的过渡扩增细胞。我们之前已经表明，鼠伤寒沙门氏菌（ST）是导致人类胃肠道感染的主要原因，它会导致小肠中的溶菌酶总体减少。为了扩展这项工作，我们在 ST 感染后的不同时间点检查小肠组织切片，以定量和定位溶菌酶的表达，并评估潘氏细胞的丰度、细胞凋亡以及潘氏细胞分化标志物的表达。响应感染，肠潘氏细胞特异性溶菌酶含量、溶菌酶阳性潘氏细胞数量和每个潘氏细胞的颗粒数量减少。然而，这伴随着隐窝中潘氏细胞总数和有丝分裂事件频率的增加，增殖标志物 PCNA 的染色增加，主要位于过渡扩增细胞所在的隐窝侧壁，而不是隐窝底部，并且在绒毛中发生凋亡事件。此外，我们发现随着时间的推移，ST 会导致第一β-连环蛋白、EphB3 和 Sox9 的上调，而感染缺乏 III 型分泌缺陷的沙门氏菌致病性岛 1 突变体时则没有观察到这种情况。我们的数据强烈表明，响应 ST 感染，启动了潘氏细胞分化程序，导致潘氏细胞群体的扩张，并且过渡扩增细胞很可能是主要祖细胞反应者。感染诱导的潘氏细胞群体扩张可能代表类似于全身感染中性粒细胞增多的急性肠道炎症反应。
