Department of Pediatrics, Division of Pediatric Infectious Diseases, Washington University School of Medicine, St Louis, MO 63110, USA.
Department of Pediatrics, Division of Pediatric Infectious Diseases, Washington University School of Medicine, St Louis, MO 63110, USA
Dis Model Mech. 2020 Mar 26;13(3):dmm043240. doi: 10.1242/dmm.043240.
represents a growing clinical threat, given its rapid development of antibiotic resistance, necessitating new therapeutic strategies. Existing live-infection models feature high mortality rates, limiting their utility in the study of natural adaptive immune response to this pathogen. We developed a preclinical model of pneumonia with low overall mortality, in which previously exposed mice are protected from subsequent respiratory tract challenge with Histologic analyses of infected murine lungs demonstrate lymphocytic aggregates surrounding vasculature and larger airways. Initial exposure in RAG1 knockout mice (lacking functional B and T cells) failed to confer protection against subsequent challenge. While administration of isolated capsule was sufficient to provide protection, we also found that initial inoculation with mutants lacking capsule (Δ), O-antigen (Δ) or both conferred protection from subsequent wild-type infection and elicited -specific antibody responses, indicating that non-capsular antigens may also elicit protective immunity. Experiments in this model will inform future development of multivalent vaccines to prevent invasive infections.
代表着一种日益严重的临床威胁，因为它对抗生素的耐药性迅速发展，需要新的治疗策略。现有的活体感染模型具有高死亡率，限制了它们在研究这种病原体对天然适应性免疫反应中的应用。我们开发了一种低总体死亡率的肺炎临床前模型，其中先前暴露的小鼠可以免受随后呼吸道接触的影响。感染小鼠肺部的组织学分析显示，血管周围和较大的气道周围有淋巴细胞聚集。在 RAG1 基因敲除小鼠（缺乏功能性 B 和 T 细胞）中的初次暴露未能提供对随后挑战的保护。虽然单独的荚膜给药足以提供保护，但我们还发现，最初接种缺乏荚膜（Δ）、O-抗原（Δ）或两者的突变体也能防止随后的野生型感染，并引发针对的抗体反应，表明非荚膜抗原也可能引发保护性免疫。该模型中的实验将为预防侵袭性感染的多价疫苗的未来发展提供信息。
