Inflammation induced by influenza virus impairs human innate immune control of pneumococcus

Area of Science:

• Immunology
• Microbiology
• Respiratory Medicine

Background:

• Pneumococcus colonization is crucial for disease and transmission, with human immune responses poorly understood.
• Loss of control during colonization, especially after influenza virus infection, can lead to secondary bacterial pneumonia.

Purpose of the Study:

• To investigate human immune responses to pneumococcus colonization and the impact of prior influenza virus infection.
• To elucidate mechanisms of pneumococcus clearance and the role of innate immunity.

Main Methods:

• Human challenge model using type 6B pneumococcus.
• Analysis of neutrophil degranulation, monocyte recruitment and function.
• Assessment of genome-wide nasal gene expression and cytokine levels (CXCL10).

Main Results:

• Pneumococcus acquisition triggered neutrophil degranulation and monocyte recruitment, with monocyte function linked to bacterial clearance.
• Prior influenza virus infection caused nasal inflammation, impaired innate immunity, and altered gene responses to pneumococcus.
• Elevated CXCL10 levels post-influenza infection correlated positively with pneumococcus bacterial load.

Conclusions:

• Human innate immune responses, particularly monocytes, are vital for controlling pneumococcus colonization.
• Influenza virus infection compromises these defenses, increasing susceptibility to pneumococcus carriage and potential secondary infections.
• CXCL10 may serve as a biomarker for impaired pneumococcus control following viral respiratory infections.