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Intraductal Injection of LPS as a Mouse Model of Mastitis: Signaling Visualized via an NF-κB Reporter Transgenic
Published on: September 4, 2012
Soluble CD14 produced by bovine mammary epithelial cells modulates their response to full length LPS
Mégane Védrine1, Florence B Gilbert1, Sarah Maman2
1ISP UMR 1282, INRAE, Université François Rabelais de Tours, Nouzilly, France.
Insights
Mammary epithelial cells secrete soluble CD14 (sCD14), crucial for recognizing Escherichia coli lipopolysaccharide (LPS). This study reveals sCD14
Area of Science:
- Veterinary Immunology
- Bovine Infectious Diseases
- Cellular Microbiology
Background:
- Bovine mastitis is a significant global cattle disease.
- Mammary epithelial cells (MECs) detect bacterial pathogens like Escherichia coli.
- Lipopolysaccharide (LPS) from E. coli is recognized by MECs via TLR4 and CD14 receptors.
Purpose of the Study:
- To investigate the role of soluble CD14 (sCD14) in MEC response to LPS.
- To determine if MECs contribute to sCD14 levels in milk.
- To elucidate the mechanisms of sCD14 in LPS recognition and downstream signaling.
Main Methods:
- Demonstration of CD14 secretion by MECs.
- Investigation of sCD14 modulation of MEC response to LPS with full-length O-antigen (LPSS).
- Analysis of Myd88-independent pathway activation.
- Identification of LPS-induced long non-coding RNAs (lncRNAs) in MECs.
Main Results:
- MECs secrete CD14, contributing to sCD14 in milk.
- sCD14 is essential for the full activation of the Myd88-independent pathway by LPSS.
- Several lncRNAs, including MIR99AHG, are activated in MECs by LPS.
Conclusions:
- MECs actively contribute to the milk sCD14 pool.
- sCD14 is indispensable for a complete MEC response to LPS.
- Milk sCD14 plays a vital role in recognizing coliform pathogens during bovine mastitis.
Abstract:
Bovine mastitis remains a major disease in cattle world-wide. In the mammary gland, mammary epithelial cells (MEC) are sentinels equipped with receptors allowing them to detect and respond to the invasion by bacterial pathogens, in particular Escherichia coli. Lipopolysaccharide (LPS) is the major E. coli motif recognized by MEC through its interaction with the TLR4 receptor and the CD14 co-receptor. Previous studies have highlighted the role of soluble CD14 (sCD14) in the efficient recognition of LPS molecules possessing a full-length O-antigen (LPSS). We demonstrate here that MEC are able to secrete CD14 and are likely to contribute to the presence of sCD14 in milk. We then investigated how sCD14 modulates and is required for the response of MEC to LPSS. This study highlights the key role of sCD14 for the full activation of the Myd88-independent pathway by LPSS. We also identified several lncRNA that are activated in MEC in response to LPS, including one lncRNA showing homologies with the mir-99a-let-7c gene (MIR99AHG). Altogether, our results show that a full response to LPS by mammary epithelial cells requires sCD14 and provide detailed information on how milk sCD14 can contribute to an efficient recognition of LPS from coliform pathogens.

