Soluble CD14 produced by bovine mammary epithelial cells modulates their response to full length LPS

Abstract

Abstract Bovine mastitis remains a major disease in cattle world-wide. In the mammary gland, epithelial cells 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 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 soluble CD14 in milk. We then investigated how CD14 modulates and is required for the response of MEC to LPSS. This study highlights the key role of soluble CD14 for the full activation of the Myd88-independent pathway by LPSS. We also identified several long non-coding RNA 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 provide detailed information on how milk soluble CD14 can contribute to an efficient recognition of LPS from coliform pathogens.