Transcriptomic Analysis of Circulating Leukocytes Obtained during the Recovery from Clinical Mastitis Caused by Escherichia coli in Holstein Dairy Cows

Abstract

The risk and severity of clinical infection with Escherichia coli as a causative pathogen for bovine mastitis is influenced by the hosts’ phenotypic and genotypic variables. We used RNA-Seq analysis of circulating leukocytes to investigate global transcriptomic profiles and genetic variants from Holstein cows with naturally occurring cases of clinical mastitis, diagnosed using clinical symptoms and milk microbiology. Healthy lactation-matched cows served as controls (CONT, n = 6). Blood samples were collected at two time periods during the recovery phase post diagnosis: EARLY (10.3 ± 1.8 days, n = 6) and LATE (46.7 ± 11 days, n = 3). Differentially expressed genes (DEGs) between the groups were identified using CLC Genomics Workbench V21 and subjected to enrichment analysis. Variant calling was performed following GATKv3.8 best practice. The comparison of E. coli(+) EARLY and CONT cows found the up-regulation of 1090 DEGs, mainly with immune and inflammatory functions. The key signalling pathways involved NOD-like and interleukin-1 receptors and chemokines. Many up-regulated DEGs encoded antimicrobial peptides including cathelicidins, beta-defensins, S100 calcium binding proteins, haptoglobin and lactoferrin. Inflammation had largely resolved in the E. coli(+) LATE group, with only 29 up-regulated DEGs. Both EARLY and LATE cows had up-regulated DEGs encoding ATP binding cassette (ABC) transporters and haemoglobin subunits were also up-regulated in LATE cows. Twelve candidate genetic variants were identified in DEGs between the infected and CONT cows. Three were in contiguous genes WIPI1, ARSG and SLC16A6 on BTA19. Two others (RAC2 and ARHGAP26) encode a Rho-family GTPase and Rho GTPase-activating protein 26. These results show that the initial inflammatory response to E. coli continued for at least 10 days despite prompt treatment and provide preliminary evidence for genetic differences between cows that may predispose them to infection.

Hepatic Global Transcriptomic Profiles of Holstein Cows According to Parity Reveal Age-Related Changes in Early Lactation

“…The downregulation of some aspects of hepatic immune function in cows from their second lactation onwards suggests that their increase in milk production in early lactation compromises immune function due to the competition for nutrients. This, in turn, would predispose these older animals to mastitis and uterine disease [ 86 , 87 , 88 , 89 ], both major risk factors leading to culling [ 9 , 90 ]. On the other hand, antimicrobial peptides were expressed at a higher level in the older cows, possibly in response to such infections.…”

Proportion of Concentrate in the Diet of Early Lactation Dairy Cows Has Contrasting Effects on Circulating Leukocyte Global Transcriptomic Profiles, Health and Fertility According to Parity

“…These can not only kill the invaded organisms directly but also assist by modulating other immune and antimicrobial processes [65][66][67]. Upregulation of antimicrobial peptides in the leukocyte transcriptomic profiles has previously been demonstrated in cows with clinical mastitis [47,68] and metritis/endometritis [69,70].…”

“…NLRs are cytosolic pattern recognition receptors which are activated by various non-self-components including bacterial peptidoglycan, potentially initiating NF-kappa B-/AP-1-dependent expression of pro-inflammatory cytokines, expression of type I interferons, autophagy and inflammation [46]. Our recent study demonstrated that this pathway was upregulated in leukocytes from E. coli-infected cows [47]. Another gene identified was MPO, encoding myeloperoxidase, an enzyme stored in azurophilic granules of PMNs and macrophages.…”

Potential of Aromatic Plant-Derived Essential Oils for the Control of Foodborne Bacteria and Antibiotic Resistance in Animal Production: A Review

“…According to an estimate, 80 species of bacteria, including E. coli and Salmonella , could pose a severe threat to poultry production [ 29 ]. Mastitis, induced by Staphylococcus aureus , Streptococcus agalactiae , Corynebacterium bovis , Streptococcus uberis , Streptococcus dysgalactiae , E. coli , Serratia marcescens and Proteus mirabilis in dairy cows, has been an economic welfare problem for dairy farms [ 30 , 31 , 32 ]. To date, many studies have reported main antibiotic resistant bacteria from different animal-derived foods in some countries, including E. coli ( Table 1 ), Salmonella spp.…”

“…ARGs and their resistance to the AGPs of E. coli , Salmonella spp., Staphylococcus spp., and Listeria spp. are shown in Table 7 [ 31 , 35 , 38 , 60 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 ]. According to the data, different species have their own ARGs.…”