Pulmonary Expression of Interleukin-17 Contributes to Neutrophil Infiltration into the Lungs during Pneumonic Plague

Area of Science:

• Microbiology
• Immunology
• Pathogenesis

Background:

• Primary pneumonic plague, caused by Yersinia pestis, is a lethal lung infection characterized by biphasic disease progression.
• The early phase involves bacterial replication without significant immune response, followed by a proinflammatory phase with cytokine upregulation and neutrophil influx.
• The Yersinia pestis virulence factor, plasminogen activator protease (Pla), is crucial for bacterial survival and virulence in the lungs.

Purpose of the Study:

• To investigate the specific host immune signals suppressed by Yersinia pestis during the preinflammatory phase of pneumonic plague.
• To elucidate the role of Interleukin-17 (IL-17) in the pathogenesis of primary pneumonic plague.
• To understand how Pla-mediated suppression of IL-17 influences disease progression.

Main Methods:

• Investigated the interaction of Pla with alveolar macrophages and the translocation of Yops via the type 3 secretion system (T3SS).
• Analyzed the impact of disrupted Pla-mediated adherence on early disease phases and neutrophil migration.
• Assessed the role of IL-17 suppression by Pla in alveolar macrophages and pulmonary neutrophils during infection.

Main Results:

• Early suppression of IL-17 by Pla in alveolar macrophages and pulmonary neutrophils limits neutrophil migration to the lungs.
• Disruption of Pla-mediated adherence leads to premature neutrophil migration.
• IL-17 contributes to neutrophil migration to the airways during the later proinflammatory phase of infection.

Conclusions:

• Early Pla-mediated suppression of IL-17 is critical for establishing the preinflammatory phase of primary pneumonic plague.
• The modulation of IL-17 expression by Yersinia pestis dictates the transition between disease phases.
• Targeting IL-17 pathways may offer therapeutic strategies against pneumonic plague.