Oehmcke-Hecht Sonja, Vasudevan Praveen, Köhler Juliane, Maletzki Claudia, Mikkat Stefan, David Robert, Kreikemeyer Bernd
Institute of Medical Microbiology, Virology and Hygiene.
Rudolf-Zenker-Institute for Experimental Surgery.
Am J Respir Cell Mol Biol. 2025 Jul;73(1):49-59. doi: 10.1165/rcmb.2024-0320OC.
(group A [GAS]) is a human pathogen that causes local and systemic infections of the skin and mucous membranes. However, GAS is also found asymptomatically in the nasopharynx of infants. GAS infections, including pharyngitis and invasive pneumosepsis, pose significant public health concerns. Streptokinase, a key virulence factor of GAS, activates human plasminogen, facilitating bacterial dissemination. Plasminogen, traditionally known for its role in fibrinolysis, may also modulate host immune responses. We therefore aim to investigate systemic and cardiac immune cell responses during pneumonia and pneumosepsis with GAS in a murine infection model. The interaction of streptokinase with human plasminogen is species specific, so the murine pneumosepsis model was developed in a transgenic mouse strain that produces human plasminogen. The data show a critical role of human plasminogen for GAS colonization and systemic spread via the nasopharynx. Because of pneumosepsis, blood immune cell profiles and plasma protein concentrations are significantly altered, indicating potential biomarkers for distinguishing local from systemic infection. In the hearts of animals with invasive infection, proinflammatory immune cells significantly increased and likely displaced resident healing macrophages. The established pneumosepsis model is useful to study the pathophysiological mechanisms underlying local and invasive pneumonia caused by GAS and to investigate new therapeutic options.
A组链球菌（GAS）是一种人类病原体，可引起皮肤和粘膜的局部及全身感染。然而，在婴儿的鼻咽部也能无症状地发现GAS。GAS感染，包括咽炎和侵袭性肺炎败血症，引起了重大的公共卫生问题。链激酶是GAS的一种关键毒力因子，可激活人纤溶酶原，促进细菌传播。纤溶酶原传统上以其在纤维蛋白溶解中的作用而闻名，它也可能调节宿主免疫反应。因此，我们旨在研究在小鼠感染模型中，GAS引起的肺炎和肺炎败血症期间的全身和心脏免疫细胞反应。链激酶与人纤溶酶原的相互作用具有物种特异性，因此在产生人纤溶酶原的转基因小鼠品系中建立了小鼠肺炎败血症模型。数据显示人纤溶酶原在GAS通过鼻咽部的定植和全身传播中起关键作用。由于肺炎败血症，血液免疫细胞谱和血浆蛋白浓度发生显著变化，这表明存在区分局部感染和全身感染的潜在生物标志物。在侵袭性感染动物的心脏中，促炎免疫细胞显著增加，并可能取代常驻的愈合巨噬细胞。已建立的肺炎败血症模型有助于研究GAS引起的局部和侵袭性肺炎的病理生理机制，并研究新的治疗选择。
