CCR5-Positive Inflammatory Monocytes are Crucial for Control of Sepsis

Area of Science:

• Immunology
• Infectious Diseases
• Cell Biology

Background:

• Neutrophils and inflammatory monocytes are key immune cells controlling sepsis through migration.
• Chemokine receptor CCR5 is typically absent on these cells but can be induced during inflammation.
• The role of CCR5 in sepsis-induced monocyte and neutrophil migration is not well understood.

Purpose of the Study:

• To investigate CCR5 expression on neutrophils and inflammatory monocytes during sepsis.
• To determine the role of CCR5 in the migration of these cells to the infectious focus.
• To elucidate the protective function of CCR5 in sepsis.

Main Methods:

• Polymicrobial sepsis was induced using the cecal ligation and puncture (CLP) model.
• Flow cytometry was used to analyze CCR5 expression on neutrophils and monocytes.
• Cell migration patterns and survival rates were assessed in wild-type and CCR5-deficient mice.

Main Results:

• CCR5 expression was induced on inflammatory monocytes (CD11b+Ly6G-Ly6C+) but not neutrophils (CD11b+Ly6G+Ly6C-) during sepsis.
• CCR5 is crucial for the migration of inflammatory monocytes from bone marrow to the circulation and infection site.
• Mice lacking CCR5 exhibited exacerbated systemic inflammation and increased mortality compared to wild-type controls.

Conclusions:

• CCR5 expression is induced on inflammatory monocytes in sepsis, facilitating their critical role in combating infection.
• CCR5 plays a significant protective role in sepsis by enabling monocyte recruitment and bacterial clearance.
• Targeting CCR5 may offer a therapeutic strategy for managing sepsis.