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

Abstract

Infections of the udder by Escherichia coli very often elicit acute inflammation, while Staphylococcus aureus infections tend to cause mild, subclinical inflammation and persistent infections. The molecular causes underlying the different disease patterns are poorly understood. We therefore profiled the kinetics and extents of global changes in the transcriptome of primary bovine mammary epithelial cells (MEC) after challenging them with heat-inactivated preparations of E. coli or S. aureus pathogens. E. coli swiftly and strongly induced an expression of cytokines and bactericidal factors. S. aureus elicited a retarded response and failed to quickly induce an expression of bactericidal factors. Both pathogens induced similar patterns of chemokines for cell recruitment into the udder, but E. coli stimulated their synthesis much faster and stronger. The genes that are exclusively and most strongly upregulated by E. coli may be clustered into a regulatory network with tumor necrosis factor alpha (TNF-␣) and interleukin-1 (IL-1) in a central position. In contrast, the expression of these master cytokines is barely regulated by S. aureus. Both pathogens quickly trigger an enhanced expression of IL-6. This is still possible after completely abrogating MyD88-dependent Toll-like receptor (TLR) signaling in MEC. The E. coli-specific strong induction of TNF-␣ and IL-1 expression may be causative for the severe inflammatory symptoms of animals suffering from E. coli mastitis, while the avoidance to quickly induce the synthesis of bactericidal factors may support the persistent survival of S. aureus within the udder. We suggest that S. aureus subverts the MyD88-dependent activation of immune gene expression in MEC.

Combined Inhibition of Complement and CD14 Efficiently Attenuated the Inflammatory Response Induced byStaphylococcus aureusin a Human Whole Blood Model

“…However, one study did not detect any IL-1b (34), whereas another claims that S. aureus does not induce TNF (35). Most studies on S. aureus have been done using the isolated cell-wall components peptidoglycan and LTA, rather than whole bacteria.…”

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

“…Identical results were reported previously for il1a (22,34), tnfa (22,26,29,31,56), and il1b (26, 29 -31, 34, 52, 56). On the contrary, Günther et al (24) showed an upregulation of il6 but not of il1a and tnfa in MEC stimulated by heat-inactivated S. aureus. The genes encoding nfkbia, nfkbiz, and rela were upregulated in cells treated with Sa and Sp, respectively.…”

“…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)(23)(24)(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.…”

“…Mammary epithelial cells (MEC) line the lumen of the mammary gland and represent the first and most abundant cell type in contact with invading bacteria and their secreted products (27). MEC have the ability to synthesize CXCL8 (24) and proinflammatory cytokines in vitro; thus they may contribute actively to the early immune and inflammatory responses of the mammary gland (25,29,30,35,43).…”

Examen critique des approches vaccinales pour lutter contre les mammites bovines

“…Si les approches classiques fondées sur l'étude des réponses à l'infection ne donnent pas de résultats satisfaisants, sur quelles connaissances peut-on fonder de nouvelles approches ? Les recherches sur le système immunitaire inné de la mamelle des ruminants ont fourni des connaissances assez développées (Aitken et al, 2011, Rainard & Riollet, 2006, et ce domaine de recherche reste actif, notamment en ce qui concerne la contribution des cellules épithéliales mammaires (Gilbert et al, 2013, Günther et al, 2011. En comparaison, les recherches sur l'immunité mammaire adaptative à médiation cellulaire, après avoir fait l'objet d'assez nombreuses études dans les années 1980-1990, sont pratiquement au point mort, et restent très lacunaires.…”