Withanage G S K, Wigley Paul, Kaiser Pete, Mastroeni Pietro, Brooks Heather, Powers Claire, Beal Richard, Barrow Paul, Maskell Duncan, McConnell Ian
Department of Veterinary Pathology, Faculty of Veterinary Science, University of Liverpool, Leahurst, Neston CH64 7TE, United Kingdom.
Infect Immun. 2005 Aug;73(8):5173-82. doi: 10.1128/IAI.73.8.5173-5182.2005.
Infection of poultry with Salmonella enterica serovar Typhimurium poses a significant risk to public health through contamination of meat from infected animals. Vaccination has been proposed to control infections in chickens. However, the vaccines are currently largely empirical, and our understanding of the mechanisms that underpin immune clearance and protection in avian salmonellosis is not complete. In this study we describe the cytokine, chemokine, and antibody responses and cellular changes in primary and secondary infections of chickens with Salmonella serovar Typhimurium. Infection of 1-week-old chickens induced early expression of a macrophage inflammatory protein (MIP) family chemokine in the spleen and liver, followed by increased expression of gamma interferon accompanied by increased numbers of both CD4(+) and CD8(+) T cells and the formation of granuloma-like follicular lesions. This response correlated with a Th1-mediated clearance of the systemic infection. Primary infection also induced specific immunoglobulin M (IgM), IgG, and IgA antibody responses. In contrast to previously published studies performed with newly hatched chicks, the expression levels of proinflammatory cytokines in the gastrointestinal tract were not greatly increased following infection. However, significant expression of the anti-inflammatory cytokine transforming growth factor beta4 was detected in the gut early in infection. Following secondary challenge, the birds were fully protected against systemic infection and showed a high level of protection against gastrointestinal colonization. Rapid expression of the MIP family chemokine and interleukin-6 was detected in the guts of these birds and was accompanied by an influx of lymphocytes. Increased levels of serum IgA-specific antibodies were also found following rechallenge. These findings suggest that cellular responses, particularly Th1 responses, play a crucial role in immune clearance in avian salmonellosis and that protection against rechallenge involves the rapid recruitment of cells to the gastrointestinal tract. Additionally, the high levels of inflammatory response found following Salmonella serovar Typhimurium infection of newly hatched chicks were not observed following infection of older birds (1 week old), in which the expression of regulatory cytokines appeared to limit inflammation.
肠炎沙门氏菌鼠伤寒血清型感染家禽会通过感染动物的肉类污染对公众健康构成重大风险。有人提议通过接种疫苗来控制鸡的感染。然而，目前的疫苗在很大程度上是经验性的，而且我们对禽沙门氏菌病中免疫清除和保护机制的理解并不完整。在本研究中，我们描述了鸡感染鼠伤寒沙门氏菌血清型后的初次和二次感染中的细胞因子、趋化因子和抗体反应以及细胞变化。1周龄鸡的感染诱导了脾脏和肝脏中巨噬细胞炎性蛋白（MIP）家族趋化因子的早期表达，随后γ干扰素表达增加，同时CD4(+)和CD8(+) T细胞数量增加，并形成肉芽肿样滤泡性病变。这种反应与Th1介导的全身感染清除相关。初次感染还诱导了特异性免疫球蛋白M（IgM）、IgG和IgA抗体反应。与之前对新孵出雏鸡进行的研究不同，感染后胃肠道中促炎细胞因子的表达水平没有大幅增加。然而，在感染早期肠道中检测到抗炎细胞因子转化生长因子β4的显著表达。二次攻击后，这些鸡对全身感染具有完全的保护作用，并且对胃肠道定植表现出高度的保护作用。在这些鸡的肠道中检测到MIP家族趋化因子和白细胞介素-6的快速表达，并伴有淋巴细胞流入。再次攻击后血清IgA特异性抗体水平也有所增加。这些发现表明，细胞反应，特别是Th1反应，在禽沙门氏菌病的免疫清除中起关键作用，并且对再次攻击的保护涉及细胞快速募集到胃肠道。此外，在1周龄的大龄鸡感染后未观察到新孵出雏鸡感染鼠伤寒沙门氏菌血清型后出现的高水平炎症反应，在大龄鸡中调节性细胞因子的表达似乎限制了炎症。
