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

Area of Science:

• Veterinary Immunology
• Bovine Pathology
• Molecular Biology

Background:

• Mastitis poses significant economic challenges in dairy farming, with Staphylococcus aureus being a primary global pathogen.
• Different S. aureus strains, such as CC151 (MOK124) causing clinical mastitis and CC97 (MOK023) causing subclinical mastitis, elicit distinct disease outcomes in Holstein-Friesian cows.

Purpose of the Study:

• To investigate the molecular mechanisms underlying the host immune response to different Staphylococcus aureus strains using a transcriptomic approach.
• To compare the gene expression profiles in milk somatic cells following infection with virulent (MOK124) and less virulent (MOK023) S. aureus strains.

Main Methods:

• Collection of milk somatic cells from experimentally infected cows at multiple time points post-infection (0, 24, 48, 72, and 168 hours post-infection).
• Differential gene expression (DE) analysis to identify genes and pathways modulated by each S. aureus strain.
• Analysis of cellular composition of milk to determine the predominant immune cell types.

Main Results:

• Both strains downregulated milk production genes, with a more pronounced effect from the MOK124 strain.
• Early immune response pathways (NF-κB, TNF) were activated by both strains, but MOK023 sustained immune pathway activation while MOK124 shifted to pathways maintaining epithelial integrity (Hippo, ECM, tight junctions).
• MOK124 infection led to a predominant neutrophil response, whereas MOK023 infection was characterized by M1 macrophages, suggesting potential immune evasion.

Conclusions:

• The host transcriptomic response to S. aureus is strain-dependent, influencing mastitis severity.
• A shift towards epithelial barrier repair pathways in the MOK124 group correlates with clinical mastitis onset.
• The MOK023 strain may employ immune evasion strategies, indicated by M1 macrophage prevalence and limited neutrophil recruitment.