Mesenteric macrophage-monocyte circuit controls systemic inflammation during enteric bacterial infection

Area of Science:

• Immunology
• Gastroenterology
• Cell Biology

Background:

• The role of the gut mesentery's immune cells in intestinal inflammation is not well understood.
• Mesentery-resident macrophages and recruited monocytes are key players in gut immunity.

Purpose of the Study:

• To define the functions of mesenteric macrophages and monocytes in Salmonella Typhimurium (STm)-induced gut inflammation.
• To elucidate the interactions between these immune cells in controlling infection.

Main Methods:

• Utilized Ccr2-deficient mice and fate-mapping techniques.
• Analyzed distinct macrophage subsets (LYVE1hi TIM4(-), LYVE1lo/- TIM4(-), LYVE1hi TIM4(+)) in the gut mesentery.
• Investigated the impact of depleting mesentery-resident macrophages.

Main Results:

• Identified two GMP-derived macrophage subsets and one embryonic-derived subset in the mesentery.
• LYVE1lo/- TIM4(-) macrophages cleared excess neutrophils; recruited monocytes produced inflammatory cytokines.
• Depletion of resident macrophages led to increased monocyte recruitment, cytokine production, and mortality during STm infection.

Conclusions:

• Mesenteric macrophage-monocyte interactions are critical for limiting systemic infection during gut inflammation.
• The mesenteric macrophage-monocyte circuit acts as a buffer against the escalation of gut infection into systemic inflammation.