Panton-valentine leucocidin carrying Staphylococcus aureus causing necrotizing pneumonia inactivates the JAK/STAT signaling pathway and increases the expression of inflammatory cytokines.

Panton-valentine leucocidin carrying Staphylococcus aureus causing necrotizing pneumonia inactivates the JAK/STAT signaling pathway and increases the expression of inflammatory cytokines.

Infect Genet Evol. 2020 Oct 02;:104582

Authors: Huang J, Zhang T, Zou X, Wu S, Zhu J

Abstract
PURPOSE: Methicillin-resistant Staphylococcus aureus (MRSA) carrying Panton-Valentine leukocidin, a pore-forming toxin, is a common cause of necrotizing pneumonia. However, the early pulmonary inflammatory response following PVL(+) MRSA infection is unknown. The purpose of this study was to use a murine model to determine the effect of PVL(+) MRSA on lung tissues and the expression of cytokines and JAK and STAT mRNA and protein.
METHODS: Mice were randomly divided into 3 groups and intra-nasally treated with PBS (control group), recombinant PVL (rPVL group), and PVL(+) MRSA (PVL group). At 24 and 48 h after inoculation, bronchoalveolar lavage fluid (BALF) was tested for cytokine levels, and lung tissues were tested for JAK and STAT mRNA and protein expression, and examined after hematoxylin and eosin staining.
RESULTS: Mice infected with the PVL(+) strain became ill, characterized by impaired mobility, hunched posture, ruffled fur, and labored breathing. Lung tissue exhibited tissue necrosis and hemorrhage. BALF levels of IL-8, TNF-α, IFN-γ, IL-12, sICAM-1, and sVCAM-1 were increased in the rPVL or PVL groups, while levels of IL-10 and IL-4 levels were similar among the groups. JAK1 and STAT1 mRNA expression and protein levels were increased in lung tissue from mice infected with PVL(+) MRSA and rPVL.
CONCLUSIONS: PVL is a significant S. aureus virulence factor, and upregulates the expression of proinflammatory cytokines but does not affect the expression of anti-inflammatory cytokines. The effect of PVL may be due to JAK/STAT pathway activation. Blockade of the JAK/STAT pathway may decrease the severity of PVL(+) MRSA pneumonia.

PMID: 33017689 [PubMed - as supplied by publisher]