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.
Mitterhuemer
Simone
S
Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Feodor-Lynen-Str 25, 81377 Munich, Germany.
Petzl
Wolfram
W
Krebs
Stefan
S
Mehne
Daniel
D
Klanner
Andrea
A
Wolf
Eckhard
E
Zerbe
Holm
H
Blum
Helmut
H
D000818:Animals; D002417:Cattle; D016000:Cluster Analysis; D019295:Computational Biology; D004927:Escherichia coli Infections / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D005260:Female; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D008321:Mammary Glands, Animal / Q000378:metabolism* / Q000382:microbiology; D008414:Mastitis, Bovine / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis