Lipopolysaccharide inhalation recruits monocytes and dendritic cell subsets to the alveolar airspace

Area of Science:

• Immunology
• Pulmonary Medicine
• Cell Biology

Background:

• Mononuclear phagocytes (MPs), including monocytes, macrophages, and dendritic cells (DCs), are vital for innate immunity and initiating adaptive immune responses.
• While MPs reside in the lungs, the recruitment dynamics of DCs during acute pulmonary inflammation remain poorly understood.

Purpose of the Study:

• To investigate the characteristics and origins of mononuclear phagocytes, particularly dendritic cells, recruited to the bronchoalveolar space during acute pulmonary inflammation in humans.
• To understand the early cellular and molecular changes in recruited MPs within the lung environment.

Main Methods:

• Induction of acute lung inflammation via lipopolysaccharide inhalation in healthy volunteers.
• Analysis of bronchoalveolar lavage fluid and blood for mononuclear phagocyte populations.
• Utilized surface phenotyping and gene expression profiling to characterize recruited cells.

Main Results:

• Lipopolysaccharide inhalation led to the expansion of classical monocytes and two specific dendritic cell subsets (DC2/3 and DC5) in bronchoalveolar lavage fluid within 8 hours.
• Evidence suggests recruited DCs are of blood origin, confirmed by surface phenotyping and gene expression analysis.
• Recruited monocytes and DCs rapidly acquired gene expression profiles typical of resident airway MPs.
• Alveolar macrophages upregulated cytokines that promote MP recruitment following lipopolysaccharide inhalation.

Conclusions:

• This study elucidates the immediate recruitment of blood-derived monocytes and dendritic cells into the bronchoalveolar space following an acute inflammatory stimulus in vivo.
• The findings highlight the rapid adaptation of these recruited cells to the lung environment and the role of alveolar macrophages in orchestrating further MP recruitment.