Bovine milk somatic cell transcriptomic response to Staphylococcus aureus is dependent on strain genotype

Abstract

Background Mastitis is an economically important disease of dairy cows with Staphylococcus aureus a major cause worldwide. Challenge of Holstein-Friesian cows demonstrated that S. aureus strain MOK124, which belongs to Clonal Complex (CC)151, caused clinical mastitis, while strain MOK023, belonging to CC97, caused mild or subclinical mastitis. The aim of this study was to elucidate the molecular mechanisms of the host immune response utilising a transcriptomic approach. Milk somatic cells were collected from cows infected with either S. aureus MOK023 or MOK124 at 0, 24, 48, 72 and 168 h post-infection (hpi) and analysed for differentially expressed (DE) genes in response to each strain. Results In response to MOK023, 1278, 2278, 1986 and 1750 DE genes were found at 24, 48, 72 and 168 hpi, respectively, while 2293, 1979, 1428 and 1544 DE genes were found in response to MOK124 at those time points. Genes involved in milk production (CSN1, CSN10, CSN1S2, CSN2, a-LACTA and PRLR) were downregulated in response to both strains, with a more pronounced decrease in the MOK124 group. Immune response pathways such as NF-κB and TNF signalling were overrepresented in response to both strains at 24 hpi. These immune pathways continued to be overrepresented in the MOK023 group at 48 and 72 hpi, while the Hippo signalling, extracellular matrix interaction (ECM) and tight junction pathways were overrepresented in the MOK124 group between 48 and 168 hpi. Cellular composition analysis demonstrated that a neutrophil response was predominant in response to MOK124, while M1 macrophages were the main milk cell type post-infection in the MOK023 group. Conclusions A switch from immune response pathways to pathways involved in maintaining the integrity of the epithelial cell layer was observed in the MOK124 group from 48 hpi, which coincided with the occurrence of clinical signs in the infected animals. The higher proportion of M1 macrophages in the MOK023 group and lack of substantial neutrophil recruitment in response to MOK023 may indicate immune evasion by this strain. The results of this study highlight that the somatic cell transcriptomic response to S. aureus is dependent on the genotype of the infecting strain.

Meta-analysis of flavonoids use into beef and dairy cattle diet: Performance, antioxidant status, ruminal fermentation, meat quality, and milk composition

“…In the present meta-analysis, lower SCC was observed in response to FLAs supplementation, indicating that FLAs improve mammary gland health and milk quality in cattle. In dairy cows, FLAs supplementation decreases the presence of Staphylococcus bacteria in milk ( 121 ), which positively correlates with SCC in ruminant milk ( 122 ). In addition, IgA has been reported to be involved in the protection of mucous membranes, IgM is the first line of defense against infections, and IgG plays an important role in the immune response against infections ( 75 , 121 ).…”

Metataxonomic analysis and host proteome response in dairy cows with high and low somatic cell count: a quarter level investigation

“…Overall, few studies up to date have explored changes in the expression and production of proteins from somatic cells during an ongoing IMI, which ultimately can be used as potential biomarkers in the diagnosis of mastitis [ 15 , 47 ]. The robustness of the immune response is highly dependent of the mastitis-causing agent and major pathogens such as streptococci, S. aureus , and coliforms can lead to a significant increase in milk SCC, whereas minor pathogens (Coryneforms and coagulase-negative staphylococci) are associated with lower SCC [ 48 ].…”

“…The efficiency of the activation of the NF-κB signaling pathway depends on the invading pathogen. Some strains of Staphylococcus aureus will induce mild and subclinical mastitis due to low production of cytokines IL-8 and IL-1β, while others will cause a higher production of these cytokines and hence clinical mastitis [ 14 , 15 ]. Gram-negative pathogens such as E. coli stimulate a strong immune response in the udder and most cases of mastitis caused by this bacterium is the severe, clinical type [ 10 ].…”

“…There are several studies available that investigate the interaction between microbes, both commensals and pathogens, in bovine milk [ 5 – 8 ]. There are also various studies that address the interaction between pathogens and the immune cells of the udder [ 15 , 19 , 20 ]. This interaction decides the outcome of the infection: clearance or establishment of the pathogen.…”

Different cellular and molecular responses of Bovine milk phagocytes to persistent and transient strains of Streptococcus uberis causing mastitis

“…coli [ 25 , 26 ] and S . aureus strains [ 27 , 28 ]. However, knowledge of the strain-specific immune response of activated milk phagocytes to S .…”