Exploring Peripheral and Cardiac Immune Responses in a Pneumosepsis Mouse Model with Group A Streptococcus.

(Group A Streptococcus, 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, therefore 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. Due to pneumosepsis blood immune cell profiles and plasma protein levels significantly alters, 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.