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A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
Baicalin protects mice from infection with methicillin-resistant Staphylococcus aureus via alleviating inflammatory
Ting Shi1,2, Tiantian Li1, Xinru Jiang1
1Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.
Abstract:
Sepsis was redefined as life-threatening organ dysfunction caused by a dysregulated host response to infection in 2016. One of its most common causes is Staphylococcus aureus, especially methicillin-resistant Staphylococcus aureus (MRSA), which leads to a significant increase in morbidity and mortality. Therefore, innovative and effective approaches to combat MRSA infection are urgently needed. Recently, host-directed therapy (HDT) has become a new strategy in the treatment of infectious diseases, especially those caused by antibiotic-resistant bacteria. Baicalin (BAI) is the predominant flavonoid and bioactive compound isolated from the roots of Radix Scutellariae (Huang Qin), a kind of traditional Chinese medicine. It has been reported that BAI exhibits multiple biological properties such as anti-oxidant, antitumor, and anti-inflammatory activities. However, the therapeutic role of BAI in MRSA infection is still unknown. In this study, it is found that BAI treatment inhibited the production of IL-6, TNF-α, and other cytokines from MRSA- or bacterial mimics-stimulated Mϕs and dendritic cells (DCs). BAI played an anti-inflammatory role by inhibiting the activation of ERK, JNK MAPK, and NF-κB pathways. Moreover, the serum level of TNF-α was decreased, whereas IL-10 was increased, in mice injected with MRSA. Furthermore, the bacterial load in livers and kidneys were further decreased by the combination of BAI and vancomycin (VAN), which might account for the amelioration of tissue damage. BAI reduced the high mortality rate caused by MRSA infection. Collectively, the results suggested that BAI may be a viable candidate of HDT strategy against severe sepsis caused by antibiotic-resistant bacteria such as MRSA.
Insights
Baicalin (BAI), a traditional Chinese medicine compound, shows promise in treating sepsis caused by methicillin-resistant Staphylococcus aureus (MRSA). BAI reduces inflammation and mortality, offering a potential host-directed therapy against antibiotic-resistant bacterial infections.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Sepsis is life-threatening organ dysfunction due to infection.
- Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of sepsis, increasing morbidity and mortality.
- Host-directed therapy (HDT) is an emerging strategy against antibiotic-resistant infections.
Purpose of the Study:
- To investigate the therapeutic role of Baicalin (BAI) in MRSA-induced sepsis.
- To explore BAI's anti-inflammatory mechanisms and its potential as an HDT.
Main Methods:
- BAI treatment effects on cytokine production in MRSA-stimulated immune cells (Mϕs, DCs).
- Analysis of inflammatory signaling pathways (ERK, JNK MAPK, NF-κB) affected by BAI.
- Assessment of BAI's impact on serum cytokine levels, bacterial load, tissue damage, and mortality in MRSA-infected mice, with and without vancomycin.
Main Results:
- BAI inhibited pro-inflammatory cytokine production (IL-6, TNF-α) in immune cells.
- BAI suppressed ERK, JNK MAPK, and NF-κB pathways, indicating an anti-inflammatory effect.
- In vivo, BAI decreased serum TNF-α, increased IL-10, reduced bacterial load in organs, ameliorated tissue damage, and lowered mortality in MRSA-infected mice.
Conclusions:
- Baicalin exhibits significant anti-inflammatory and anti-sepsis effects against MRSA infection.
- BAI demonstrates potential as a host-directed therapy, particularly in combination with antibiotics like vancomycin.
- BAI represents a promising candidate for combating severe sepsis caused by antibiotic-resistant bacteria.

