Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.165, 3508 TD Utrecht, The Netherlands.
Vet Microbiol. 2012 Dec 7;160(3-4):347-54. doi: 10.1016/j.vetmic.2012.05.034. Epub 2012 Jun 7.
Little is known about the interactions of chicken host defense peptides (HDPs) with Campylobacter jejuni in young chicks. To examine the role of the chicken HDP, cathelicidin-2 (CATH-2) in host-pathogen interactions we challenged 4-day-old Ross 308 broilers with a chicken-derived C. jejuni isolate (WS356) and used the chicken pathogen Salmonella enterica Enteritidis phage type 4 (FGT1) as a reference. Immunohistochemical staining was used to localize CATH-2, C. jejuni and Salmonella enteritidis. Intestinal CATH-2 mRNA expression levels were determined by quantitative PCR. Antibacterial activities of CATH-2 peptide against C. jejuni and S. enteritidis isolates were assessed in colony count assays. In contrast to S. enteritidis, C. jejuni was not seen to attach to intestinal epithelium and C. jejuni challenge did not result in recruitment of CATH-2 containing heterophils to the small intestinal lamina propria. Minimal inhibitory concentrations found for CATH-2 peptide against human- and chicken-derived C. jejuni isolates were similar (0.6-2.5 μM) and much lower than for S. enteritidis (20 μM). Compared to wild-type C. jejuni 81116, the lipooligosaccharide (LOS)-deficient 81116ΔwaaF mutant was much more susceptible to CATH-2. Interestingly, CATH-2 mRNA expression levels in the small intestine were significantly lower 48 h p.i. in C. jejuni-challenged chicks. These findings indicate that human clinical and chicken-derived C. jejuni are equally highly susceptible to chicken CATH-2 peptide and that C. jejuni uses LOS to protect itself to some extent against HDPs. Moreover, suppression of intestinal CATH-2 expression levels may be part of the C. jejuni immune evasion strategy.
关于鸡宿主防御肽（HDPs）与空肠弯曲菌之间相互作用的知之甚少。为了研究鸡 HDP 、 cathelicidin-2（CATH-2）在宿主-病原体相互作用中的作用，我们用鸡源空肠弯曲菌分离株（WS356）挑战了 4 日龄的 Ross 308 肉鸡，并使用鸡病原体肠炎沙门氏菌肠型 4（FGT1）作为参考。免疫组织化学染色用于定位 CATH-2、空肠弯曲菌和肠炎沙门氏菌。通过定量 PCR 测定肠道 CATH-2 mRNA 表达水平。通过集落计数测定评估 CATH-2 肽对空肠弯曲菌和肠炎沙门氏菌分离株的抗菌活性。与肠炎沙门氏菌不同，空肠弯曲菌未被观察到附着在肠上皮上，空肠弯曲菌的挑战也没有导致含 CATH-2 的异嗜性粒细胞募集到小肠固有层。发现 CATH-2 肽对人源和鸡源空肠弯曲菌分离株的最小抑菌浓度相似（0.6-2.5 μM），远低于肠炎沙门氏菌（20 μM）。与野生型空肠弯曲菌 81116 相比，脂寡糖（LOS）缺陷型 81116ΔwaaF 突变体对 CATH-2 更敏感。有趣的是，空肠弯曲菌感染后 48 小时，空肠弯曲菌感染的小鸡小肠中 CATH-2 mRNA 表达水平显著降低。这些发现表明，人类临床和鸡源空肠弯曲菌对鸡 CATH-2 肽同样高度敏感，空肠弯曲菌在某种程度上使用 LOS 来保护自己免受 HDPs 的侵害。此外，抑制肠道 CATH-2 表达水平可能是空肠弯曲菌免疫逃避策略的一部分。
