Abstract
ObjectivesThe 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 MethodsWe 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.ResultsAfter 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.ConclusionsThis study provides evidence for the involvement of MCs in the regulation of the lung‐gut axis during S. aureus pneumonia.
Highlights
Staphylococcus aureus is one of the common pathogens in hos‐ pital‐ and community‐acquired pneumonia.[1]
In this study, using Mast cells (MCs)‐ deficient mice (KitW‐sh/W‐sh) with defective c‐kit receptor, we evaluated the diversity of the intestinal microbial community in mice with S. au‐ reus pneumonia and determined the role of MCs in regulation of the lung‐gut axis
We showed that MC deficiency impaired lung inflamma‐ tion and aggravated the imbalance in the gut microbiota upon S. aureus infection
Summary
Staphylococcus aureus is one of the common pathogens in hos‐ pital‐ and community‐acquired pneumonia.[1]. Mast cells (MCs) are abundant at host‐environment interfaces, such as the skin and the respiratory and gastrointestinal tracts Because of their location, MCs have been hypothesized to act as sentinel cells that sense pathogen attacks and initiate a pro‐ tective immune response.[5]. In this study, using MC‐ deficient mice (KitW‐sh/W‐sh) with defective c‐kit receptor, we evaluated the diversity of the intestinal microbial community in mice with S. au‐ reus pneumonia and determined the role of MCs in regulation of the lung‐gut axis. Adoptive transfer of bone marrow mast cells (BMMCs) into the lung largely reconstituted the host defence against S. aureus in both the lung and the gut, demonstrating a critical role of MCs in the immune response through regulation of the lung‐gut axis
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