The Impact of Intramammary Escherichia coli Challenge on Liver and Mammary Transcriptome and Cross-Talk in Dairy Cows during Early Lactation Using RNAseq.

K. M. Moyes,P. Sørensen,M. Bionaz,Ramona Natacha PENA i SUBIRÀ

doi:10.1371/journal.pone.0157480

K. M. Moyes, P. Sørensen + Show 2 more

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https://doi.org/10.1371/journal.pone.0157480

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Abstract

Our objective was to identify the biological response and the cross-talk between liver and mammary tissue after intramammary infection (IMI) with Escherichia coli (E. coli) using RNAseq technology. Sixteen cows were inoculated with live E. coli into one mammary quarter at ~4–6 weeks in lactation. For all cows, biopsies were performed at -144, 12 and 24 h relative to IMI in liver and at 24 h post-IMI in infected and non-infected (control) mammary quarters. For a subset of cows (n = 6), RNA was extracted from both liver and mammary tissue and sequenced using a 100 bp paired-end approach. Ingenuity Pathway Analysis and the Dynamic Impact Approach analysis of differentially expressed genes (overall effect False Discovery Rate≤0.05) indicated that IMI induced an overall activation of inflammation at 12 h post-IMI and a strong inhibition of metabolism, especially related to lipid, glucose, and xenobiotics at 24 h post-IMI in liver. The data indicated in mammary tissue an overall induction of inflammatory response with little effect on metabolism at 24 h post-IMI. We identified a large number of up-stream regulators potentially involved in the response to IMI in both tissues but a relatively small core network of transcription factors controlling the response to IMI for liver whereas a large network in mammary tissue. Transcriptomic results in liver and mammary tissue were supported by changes in inflammatory and metabolic mediators in blood and milk. The analysis of potential cross-talk between the two tissues during IMI uncovered a large communication from the mammary tissue to the liver to coordinate the inflammatory response but a relatively small communication from the liver to the mammary tissue. Our results indicate a strong induction of the inflammatory response in mammary tissue and impairment of liver metabolism 24h post-IMI partly driven by the signaling from infected mammary tissue.

Highlights

During early lactation, the massive repartition of nutrients to the mammary gland for milk synthesis has been identified as a major contributor to the high risk of developing diseases [1]
Change in concentration of alkaline phosphatase (AP), NAGase and lactate dehydrogenase (LDH) in milk after intramammary infection (IMI) with E. coli for all 16 cows is shown in S1 Fig. Alkaline phosphatase increased by 48 h after IMI when compared to pre-IMI levels (h = 0)
Feed intake and milk yield response for cows (n = 16) after IMI challenge with E. coli are shown in S2 Fig. Feed intake decreased by 48 h post-IMI and returned to pre-IMI levels by 72 h post-IMI whereas milk yield decreased by 24 h, remained lower through 48 h, and returned to pre-IMI levels by 60 h post-IMI

Summary

Introduction

During early lactation (i.e. the first 60 days of lactation), the massive repartition of nutrients to the mammary gland for milk synthesis has been identified as a major contributor to the high risk of developing diseases [1]. The requirement of energy and nutrients increases ~5-fold from pregnancy to lactation in high producing dairy cows mainly due to the large amount of milk synthesized by the mammary gland [2]. Besides its vital role in metabolism, the liver participates to the immune response by synthesizing and secreting into the bloodstream inflammatory mediators (i.e. acute phase proteins) [5]. During inflammatory states such as mastitis, the immunometabolic demands may compromise liver function and increase risk of disease

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