Mast cells participate in regulation of lung-gut axis during Staphylococcus aureus pneumonia

Abstract

Objectives: The lung-gut axis is known to be involved in the pathogenesis of Staphylococcus aureus pneumonia. However, the underlying mechanisms remain unclear. We examined the role of pulmonary mast cells (MCs) in the regulation of the lung-gut axis during S. aureus pneumonia.

Materials and methods: We created a mouse model of S. aureus pneumonia using MC-deficient mice (Kit^W-sh/W-sh ) and examined the level of inflammation, bacterial burden, expression of cathelicidin-related antimicrobial peptide (CRAMP) and composition of the gut microbiota. We further evaluated anti-bacterial immunity by administering bone marrow MCs (BMMCs) or CRAMP into the lungs of Kit^W-sh/W-sh mice.

Results: After S. aureus challenge, the MC-deficient mice, compared with wild-type (WT) mice, displayed attenuated lung inflammation, decreased expression of CRAMP, higher bacterial lung load and disturbance of the intestinal microbiota. Adoptive transfer of BMMCs into the lung effectively reconstituted the host defence against S. aureus in Kit^W-sh/W-sh mice, thus resulting in recovery of S. aureus pneumonia-induced intestinal dysfunction. Similarly, exogenous administration of CRAMP significantly enhanced anti-bacterial immunity in the lungs of MC-deficient mice.

Conclusions: This study provides evidence for the involvement of MCs in the regulation of the lung-gut axis during S. aureus pneumonia.

Keywords: Staphylococcus aureus pneumonia; intestinal microbiota; lung-gut axis; mast cells.