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

Abstract

BackgroundColiform 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.ResultsAfter 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.ConclusionsThe 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.

Effects of combined liver and udder biopsying on the acute phase response of dairy cows with experimentally induced E. coli mastitis

“…The subsequent elevated body temperature (fever), heart rate and respiration rates following the E. coli inoculation were within the same time frame (12 to 18 h PI) as reported by others (Blum et al, 2000;Suojala et al, 2008;Mitterhuemer et al, 2010). Furthermore, E. coli mastitis significantly lowered rumen motility as described by Pezeshki et al (2011).…”

“…Opposite SCC, we found a significantly higher MAA level that was induced directly or indirectly by injuries inflicted by biopsying the udder. MAA, also known as SAA isotype 3, is produced extrahepatically not only in organs such as the udder (Jacobsen et al, 2005;Mitterhuemer et al, 2010) but also in the liver (Vels et al, 2009). Indeed, the higher level of E. coli in milk of the biopsied cows is likely to have contributed to the additional increase in the MAA concentration as bacteria count, and the degree of tissue trauma was shown to be correlated with the level of MAA (Jacobsen et al, 2005).…”

“…E. coli mastitis induces a local and systemic acute phase response (APR) in the infected cows (Suojala et al, 2008;Mitterhuemer et al, 2010). The APR -Present address: CMR On-Site RD, Skjernvej 4A, DK-9220 Aalborg Øst, Denmark.…”

Interferon stimulated genes as peripheral diagnostic markers of early pregnancy in sheep: a critical assessment

“…Bacterial infection of the mammary gland is locally characterized by neutrophilic inflammation, resulting in production of a large amount of interleukins and cytokines, including ISG (Rainard et al, 2013). Besides this local reaction, inflammatory response to mastitis involves systemic consequences such as leucocyte activation (Jiang et al, 2008) and enhanced expression of antimicrobial and cytokine genes (Mitterhuemer et al, 2010). In commercial herds, prevalence of these subclinical diseases might restrict the relevance of ISG as biomarkers of early pregnancy to nulliparous ewes or heifers, which have not been affected by endometritis or mastitis.…”

Bovine P-selectin mediates leukocyte adhesion and is highly polymorphic in dairy breeds

“…The efficiency of the host defense system plays a major role in the ability to deal with mastitis-causing pathogens, and thus ultimately in determining the severity of infection (Burvenich et al, 2003;Rainard and Riollet, 2006). We recently undertook a combined analysis of data from seven published genome-wide association studies (GWAS) on milk somatic cell count (SCC) together with two experiments reporting changes in gene expression in the mammary gland following experimental infection with either E. coli or S. uberis (Chen et al, 2015;Mitterhuemer et al, 2010;Moyes et al, 2009) to determine key pathways involved in the host response. In support of previous work, this approach again highlighted the importance of the leukocyte adhesion/diapedesis signaling pathway in combatting mammary gland infection, by assisting a timely influx of polymorphonuclear leukocytes (PMN) to the infected udder (Paape et al, 2002).…”