Influence of systemic inflammatory response syndrome on host resistance against bacterial infections

Area of Science:

• Immunology
• Infectious Diseases
• Critical Care Medicine

Background:

• Systemic inflammatory response syndrome (SIRS) is a complex clinical condition with significant implications for host defense.
• Understanding the interplay between SIRS and innate immunity is crucial for managing bacterial infections in critically ill patients.
• Previous research has not fully elucidated how different SIRS severity levels modulate specific immune cell functions relevant to combating bacterial pathogens.

Purpose of the Study:

• To investigate the relationship between varying degrees of SIRS and the host's innate immune capacity to fight bacterial infections.
• To compare the susceptibility and immune responses of mice with mild versus severe SIRS to common bacterial pathogens and sepsis models.
• To characterize the functional properties of immune effector cells, specifically macrophages, derived from mice with different SIRS severities.

Main Methods:

• A controlled animal study was conducted using male BALB/c mice.
• Mice were subjected to conditions inducing mild or severe SIRS, followed by infection with Enterococcus faecalis, methicillin-resistant Staphylococcus aureus (MRSA), or cecal ligation and puncture (CLP) to induce sepsis.
• The function of antibacterial innate immune effector cells was assessed, including experiments with severe combined immunodeficient beige nude mice (SCIDbgMN) reconstituted with macrophages from SIRS mice.

Main Results:

• Mice with severe SIRS exhibited significantly higher susceptibility and mortality rates to E. faecalis, MRSA, and CLP-induced sepsis compared to normal mice.
• Conversely, mice with mild SIRS demonstrated resistance to these infections.
• Peritoneal macrophages (PMphi) from mild SIRS mice conferred protection against infection in SCIDbgMN mice, exhibiting characteristics of classically activated macrophages (CAMphi), whereas PMphi from severe SIRS mice did not confer protection and displayed properties of alternatively activated macrophages (AAMphi).

Conclusions:

• Host antibacterial innate immunity is profoundly influenced by the severity of SIRS.
• Mild SIRS induces CAMphi, which are essential for effective defense against E. faecalis, MRSA, and sepsis.
• Severe SIRS leads to the generation of AAMphi, which lack antibacterial capabilities, suggesting that strategies to induce CAMphi could be beneficial for patients with severe SIRS and infections.