Staphylococcus aureuslipoteichoic acid triggers inflammation in the lactating bovine mammary gland

Abstract

-The response of the bovine mammary gland to lipoteichoic acid (LTA), which is a major pathogen-associated molecular pattern of Gram-positive bacteria, was investigated by infusing purified Staphylococcus aureus LTA in the lumen of the gland. LTA was able to induce clinical mastitis at the dose of 100 g/quarter, and a subclinical inflammatory response at 10 g/quarter. The induced inflammation was characterized by a prompt and massive influx of neutrophils in milk. LTA proved to induce strongly the secretion of the chemokines CXCL1, CXCL2, CXCL3 and CXCL8, which target mainly neutrophils. The complement-derived chemoattractant C5a was generated in milk only with the highest dose of LTA (100 g). The pro-inflammatory cytokine IL-1 was induced in milk, but there was very little if any TNF-and no IFN-. The re-assessment of CXCL8 concentrations in milk whey of quarters previously challenged with S. aureus, by using an ELISA designed for bovine CXCL8, showed that this chemokine was induced in milk, contradicting previous reports. Overall, S. aureus LTA elicited mammary inflammatory responses that shared several attributes with S. aureus mastitis. Purified LTA looks promising as a convenient tool to investigate the inflammatory and immune responses of the mammary gland to S. aureus. Staphylococcus aureus / mastitis / cattle / lipoteichoic acid / chemokine

Genetic susceptibility to S. aureus mastitis in sheep: differential expression of mammary epithelial cells in response to live bacteria or supernatant

“…Overexpression of CXCL3 and CXCL8 was also detected at the protein levels. The upregulation of these chemokines was also demonstrated in MEC after LTA stimulation (13,41) or after contact with Sa (29,30,34). These results support the idea that MEC attract neutrophils in the mammary gland in the presence of S. aureus (3,17).…”

“…To offset part of these issues, in vitro models of MEC cultures have been largely used to study the interaction of Escherichia coli or S. aureus with the host cells (11,22,25,29,52,58). Although the interaction of MEC with live bacteria has already been studied in several reports (29,31,34), heat-killed bacteria (22-25) and pathogen-associated molecular patterns (PAMP), such as lipopolysaccharide (LPS) for E. coli or lipoteichoic acid (LTA) for S. aureus (1,11,13,30,37,41,58) or supernatant (Sp) (34), are more commonly used. The recourse to synthetic or inert stimuli avoids bacterial development in the culture medium and ensuing consumption of nutrients by the bacteria or release of highly toxic compounds.…”

Comparative Kinetics ofEscherichia coli- andStaphylococcus aureus-Specific Activation of Key Immune Pathways in Mammary Epithelial Cells Demonstrates ThatS. aureusElicits a Delayed Response Dominated by Interleukin-6 (IL-6) but Not by IL-1A or Tumor Necrosis Factor Alpha

“…Our observation of a much weaker induction of inflammatory mediators by S. aureus-infected udders has frequently been observed for cows suffering from S. aureus mastitis (4,39,40). Moreover, S. aureus infection was previously found to cause only modest changes (Ͻ4-fold-changed mRNA concentrations) in the global transcriptome of milk cells from goats (36).…”

Lactobacillus plantarum Lipoteichoic Acid Alleviates TNF-α-Induced Inflammation in the HT-29 Intestinal Epithelial Cell Line

“…LTA is a cell wall component of Gram-positive bacteria that has numerous biological functions including neutrophil recruitment, impairment of osteoclastogenesis, and induction of inflammation in the mammary gland and lung. It also causes septic shock and multiorgan failure (Bougarn et al, 2010;De Kimpe et al, 1995;Knapp et al, 2008;Rainard et al, 2008;Yang et al, 2009). LTA plays important roles in both innate and adaptive immunity (Chan et al, 2007;Kim et al, 2007b;Seo et al, 2008).…”