Escherichia coli infection induces distinct local and systemic transcriptome responses in the mammary gland

Background: Coliform bacteria are the most common etiologic agents
in severe mastitis of cows. Escherichia coli infections are mostly
restricted to a single udder quarter whereas neighboring quarters
stay clinically inapparent, implicating the presence of a systemic
defense reaction. To address its underlying mechanism, we performed
a transcriptome study of mammary tissue from udder quarters
inoculated with E. coli (6 h and 24 h post infection), from
neighboring quarters of the same animals, and from untreated
control animals. Results: After 6 h 13 probe sets of differentially
expressed genes (DEG) were detected in infected quarters versus
control animals. Eighteen hours later 2154 and 476 DEG were found
in infected and in neighboring quarters vs. control animals.
Cluster analysis revealed DEG found only in infected quarters
(local response) and DEG detected in both infected and neighboring
quarters (systemic response). The first group includes genes mainly
involved in immune response and inflammation, while the systemic
reaction comprises antigen processing and presentation, cytokines,
protein degradation and apoptosis. Enhanced expression of
antimicrobial genes (S100A8, S100A9, S100A12, CXCL2, GNLY), acute
phase genes (LBP, SAA3, CP, BF, C6, C4BPA, IF), and indicators of
oxidative stress (GPX3, MT1A, MT2A, SOD2) point to an active
defense reaction in infected and neighboring healthy quarters. Its
early onset is indicated by increased transcription of NFIL3 at 6
h. NFIL3 is a predicted regulator of many genes of the systemic
response at 24 h. The significance of our transcriptome study was
evidenced by some recent findings with candidate gene based
approaches. Conclusions: The discovery and holistic analysis of an
extensive systemic reaction in the mammary gland significantly
expands the knowledge of host-pathogen interactions in mastitis
which may be relevant for the development of novel therapies and
for genetic selection towards mastitis resistance.