Transitional premonocytes emerge in the periphery for host defense against bacterial infections

Area of Science:

• Immunology
• Cell Biology
• Infectious Disease

Background:

• Circulating Ly6C-hi monocytes are crucial for antibacterial defense but undergo apoptosis upon exhaustion, limiting macrophage replenishment.
• The mechanisms for replacing tissue-resident macrophages during bacterial infections remain unclear, impacting host defense and infection morbidity.

Purpose of the Study:

• To investigate the role of monocyte precursors in macrophage replenishment during bacterial infection and sepsis.
• To determine if transitional premonocytes (TpMos) can serve as an alternative source of macrophages to combat infection.

Main Methods:

• Mobilization of TpMos into the periphery during acute bacterial infection and sepsis models.
• Assessment of TpMo susceptibility to apoptosis compared to mature Ly6C-hi monocytes (MatMos).
• Evaluation of TpMo-derived macrophages in host defense and cytokine response modulation.
• Analysis of adoptive transfer of TpMos in a lethal sepsis model.

Main Results:

• TpMos were mobilized into the periphery in response to bacterial infection and sepsis.
• TpMos exhibited lower susceptibility to apoptosis than MatMos.
• TpMos served as the primary source for macrophage replenishment when MatMos were vulnerable.
• TpMo-derived macrophages helped balance the pro-inflammatory cytokine response.
• Adoptive transfer of TpMos significantly improved survival in a lethal sepsis model.

Conclusions:

• TpMos play a critical protective role in bacterial infections by replenishing macrophages.
• TpMos contribute to monocyte-derived macrophage heterogeneity, influencing disease outcomes.
• TpMos represent a promising therapeutic target for enhancing host defense against bacterial infections and sepsis.