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Exploring Peripheral and Cardiac Immune Responses in a Pneumosepsis Mouse Model with Group A Streptococcus
Sonja Oehmcke-Hecht1, Praveen Vasudevan2, Juliane Köhler1
1Institute of Medical Microbiology, Virology and Hygiene.
Insights
Streptococcus pyogenes (GAS) uses human plasminogen to spread. This study reveals how GAS causes invasive pneumosepsis and identifies potential biomarkers for infection.
Area of Science:
- * Microbiology and Immunology
- * Pathogen-host interactions
Background:
- * Streptococcus pyogenes (Group A Streptococcus, GAS) is a significant human pathogen causing diverse infections.
- * GAS colonization in the nasopharynx can lead to severe conditions like pneumosepsis.
- * Streptokinase, a GAS virulence factor, activates human plasminogen, aiding bacterial spread and potentially influencing immune responses.
Purpose of the Study:
- * To investigate systemic and cardiac immune cell responses during GAS pneumonia and pneumosepsis.
- * To explore the role of human plasminogen in GAS infection dynamics.
- * To identify potential biomarkers for differentiating local versus systemic GAS infections.
Main Methods:
- * Development of a murine pneumosepsis model using a transgenic mouse strain expressing human plasminogen.
- * Analysis of blood immune cell profiles and plasma protein levels.
- * Examination of cardiac immune cell infiltration in infected animals.
Main Results:
- * Human plasminogen is critical for GAS colonization and systemic dissemination from the nasopharynx.
- * Pneumosepsis significantly alters blood immune cell and plasma protein profiles, suggesting potential diagnostic biomarkers.
- * Invasive infections lead to increased pro-inflammatory immune cells in the heart, potentially displacing resident macrophages.
Conclusions:
- * The developed murine model is effective for studying GAS pneumonia and pneumosepsis pathophysiology.
- * Human plasminogen plays a crucial role in GAS systemic spread.
- * Immune cell changes in blood and heart offer insights into infection severity and potential therapeutic targets.
Abstract:
Streptococcus pyogenes (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, 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.
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