scholarly journals Translational study of the whole transcriptome in rats and genetic polymorphisms in humans identifies LRP1B and VPS13A as key genes involved in tolerance to cocaine-induced motor disturbances

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Florence Vorspan ◽  
Romain Icick ◽  
Nawel Mekdad ◽  
Cindie Courtin ◽  
Vanessa Bloch ◽  
...  
Keyword(s):  
Dorsal Striatum ◽  
Differentially Expressed ◽  
Comprehensive Description ◽  
Transcriptomic Response ◽  
Cocaine Use ◽  
Translational Study ◽  
Motor Effects ◽  
Whole Transcriptome ◽  
Significant Protective Effect ◽  
Motor Disturbances

Abstract Motor disturbances strongly increase the burden of cocaine use disorder (CUDs). The objective of our translational study was to identify the genes and biological pathways underlying the tolerance to cocaine-induced motor effects. In a 5-day protocol measuring motor tolerance to cocaine in rats (N = 40), modeling the motor response to cocaine in patients, whole-genome RNA sequencing was conducted on the ventral and dorsal striatum to prioritize a genetic association study in 225 patients with severe CUD who underwent thorough phenotypic (cocaine-induced hyperlocomotion, CIH; and cocaine-induced stereotypies, CIS) and genotypic [571,000 polymorphisms (SNPs)] characterization. We provide a comprehensive description of the rat striatal transcriptomic response to cocaine in our paradigm. Repeated vs. acute cocaine binge administration elicited 27 differentially expressed genes in the ventral striatum and two in the dorsal striatum. One gene, Lrp1b, was differentially expressed in both regions. In patients, LRP1B was significantly associated with both CIS and CIH. CIH was also associated with VPS13A, a gene involved in a severe neurological disorder characterized by hyperkinetic movements. The LRP1B minor allele rs7568970 had a significant protective effect against CIS (558 SNPs, Bonferroni-corrected p = 0.02) that resisted adjustment for confounding factors, including the amount of cocaine use (adjusted beta = −0.965 and −2.35 for heterozygotes and homozygotes, respectively, p < 0.01). Using hypothesis-free prioritization of candidate genes along with thorough methodology in both the preclinical and human analysis pipelines, we provide reliable evidence that LRP1B and VPS13A are involved in the motor tolerance to cocaine in CUD patients, in line with their known pathophysiology.

scholarly journals Copper Availability Influences the Transcriptomic Response of Candida albicans to Fluconazole Stress

2021 ◽  
Vol 11 (4) ◽  
Author(s):  
Elizabeth W Hunsaker ◽  
Chen-Hsin Albert Yu ◽  
Katherine J Franz
Keyword(s):  
Candida Albicans ◽  
Time Course ◽  
Transcriptional Response ◽  
Metal Homeostasis ◽  
Metal Availability ◽  
Drug Induced ◽  
Transcriptomic Response ◽  
Opportunistic Fungal Pathogen ◽  
Whole Transcriptome Analysis ◽  
Whole Transcriptome

Abstract The ability of pathogens to maintain homeostatic levels of essential biometals is known to be important for survival and virulence in a host, which itself regulates metal availability as part of its response to infection. Given this importance of metal homeostasis, we sought to address how the availability of copper in particular impacts the response of the opportunistic fungal pathogen Candida albicans to treatment with the antifungal drug fluconazole. The present study reports whole transcriptome analysis via time-course RNA-seq of C. albicans cells exposed to fluconazole with and without 10 µM supplemental CuSO4 added to the growth medium. The results show widespread impacts of small changes in Cu availability on the transcriptional response of C. albicans to fluconazole. Of the 2359 genes that were differentially expressed under conditions of cotreatment, 50% were found to be driven uniquely by exposure to both Cu and fluconazole. The breadth of metabolic processes that were affected by cotreatment illuminates a fundamental intersectionality between Cu metabolism and fungal response to drug stress. More generally, these results show that seemingly minor fluctuations in Cu availability are sufficient to shift cells’ transcriptional response to drug stress. Ultimately, the findings may inform the development of new strategies that capitalize on drug-induced vulnerabilities in metal homeostasis pathways.

scholarly journals Identification and characterization of differentially expressed genes in Caenorhabditis elegans in response to pathogenic and nonpathogenic Stenotrophomonas maltophilia

2019 ◽  
Author(s):  
Leah J Radeke ◽  
Michael Herman
Keyword(s):  
Candidate Genes ◽  
Differentially Expressed Genes ◽  
Stenotrophomonas Maltophilia ◽  
Defense Mechanisms ◽  
Virulent Strain ◽  
Differentially Expressed ◽  
Transcriptional Responses ◽  
Transcriptomic Response ◽  
C Elegans ◽  
Realistic Interaction

Abstract Background: Stenotrophomonas maltophilia is an emerging nosocomial pathogen that causes infection in immunocompromised patients. S. maltophilia isolates are genetically diverse, contain diverse virulence factors, and are variably pathogenic within several host species. Members of the Stenotrophomonas genus are part of the native microbiome of C. elegans , being found in greater relative abundance within the worm than its environment, suggesting that these bacteria accumulate within C. elegans . Thus, study of the C. elegans-Stenotrophomonas interaction is of both medical and ecological significance. To identify host defense mechanisms, we analyzed the C. elegans transcriptomic response to S. maltophilia strains of varying pathogenicity: K279a, an avirulent clinical isolate, JCMS, a virulent strain isolated in association with soil nematodes near Manhattan, KS, and JV3, an even more virulent environmental isolate. Results: Overall, we found 145 genes that are commonly differentially expressed in response to pathogenic S. maltophilia strains, 89% of which are upregulated, with many even further upregulated in response to JV3 as compared to JCMS. There are many more JV3-specific differentially expressed genes (225, 11% upregulated) than JCMS-specific differentially expressed genes (14, 86% upregulated), suggesting JV3 has unique pathogenic mechanisms that could explain its increased virulence. We used connectivity within a gene network model to choose pathogen-specific and strain-specific differentially expressed candidate genes for functional analysis. Mutations in 13 of 22 candidate genes caused significant differences in C. elegans survival in response to at least one S. maltophilia strain, although not always the strain that induced differential expression, suggesting a dynamic response to varying levels of pathogenicity. Conclusions: Variation in observed pathogenicity and differences in host transcriptional responses to S. maltophilia strains reveal that strain-specific mechanisms play important roles in S. maltophilia pathogenesis. Furthermore, utilizing bacteria closely related to strains found in C. elegans natural environment provides a more realistic interaction for understanding host-pathogen response.

Whole Transcriptome Analysis: Implication to Estrous Cycle Regulation

2021 ◽  
Author(s):  
Xiaopeng An ◽  
Yue Zhang ◽  
Fu Li ◽  
Zhanhang Wang ◽  
Shaohua Yang ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Transcriptome Analysis ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Whole Transcriptome Analysis ◽  
Cycle Regulation ◽  
Whole Transcriptome ◽  
Goat Ovary

Abstract BackgroundEstrous cycle is one of female characteristics after sexual maturity, including estrus (ES) and diestrus (DS) stages. Estrous cycle is important in female physiology and its disorder may lead to diseases. In the latest years, effects of non-coding RNAs and mRNA on estrous cycle start to arouse much concern, however, a whole transcriptome analysis among non-coding RNAs and mRNA has not been reported.ResultsHere we report a whole transcriptome analysis of goat ovary in estrus and diestrus periods. Estrus synchronization was conducted to induce the estrus phase and on day 32, the goats naturally shifted into diestrus stage. The ovary RNA of estrus and diestrus stages was respectively collected to perform RNA-sequencing. Then the circular RNA; microRNA; long non-coding RNA; mRNA databases of goat ovary were acquired, and the differentially expressions between estrus and diestrus stages were screened to construct circRNA-miRNA-mRNA/lncRNA and lncRNA-miRNA/mRNA networks, thus providing potential pathways that involved in the regulation of estrous cycle. Differentially expressed mRNAs, such as MMP9, TIMP1, 3BHSD and PTGIS, and differentially expressed microRNAs, such as miR-21-3p，miR-202-3p and miR-223-3p, which play key roles in estrous cycle regulation were extracted from the network.ConclusionsOur data provided the miRNA, circRNA, lncRNA and mRNA databases of goat ovary and each differentially expressed profile between ES and DS. Networks among differentially expressed miRNAs, circRNAs, lncRNAs and mRNAs were constructed to provide valuable resources for the study of estrous cycle and related diseases.

scholarly journals Phenotypic and transcriptomic responses of cultivated sunflower seedlings (Helianthus annuus L.) to four abiotic stresses

2021 ◽  
Author(s):  
Max H. Barnhart ◽  
Rishi R. Masalia ◽  
Liana J. Mosley ◽  
John M. Burke
Keyword(s):  
Helianthus Annuus ◽  
Abiotic Stresses ◽  
Differential Expression Analysis ◽  
Leaf Tissue ◽  
Belowground Biomass ◽  
Nutrient Stress ◽  
Differentially Expressed ◽  
Transcriptomic Response ◽  
Multiple Stresses ◽  
Dry Down

Abstract Plants encounter and respond to numerous abiotic stresses during their lifetimes. These stresses are often related and could therefore elicit related responses. There are, however, relatively few detailed comparisons between multiple different stresses at the molecular level. Here, we investigated the phenotypic and transcriptomic response of cultivated sunflower (Helianthus annuus L.) seedlings to three water-related stresses (i.e., dry-down, an osmotic challenge with polyethylene glycol 6000 [PEG], and salt stress), as well as a generalized low-nutrient stress. Our goal was to identify commonalities in the response to the three water-related stresses and compare them to a distinct low-nutrient stress. All four stresses negatively impacted seedling growth, with the low-nutrient stress having a more divergent response from control as compared to the water-related stresses. Observed phenotypic responses were consistent with expectation for growth in low-resource environments, including increased (i.e., less negative) carbon fractionation values and leaf C:N ratios, as well as increased belowground biomass allocation. Analysis of the leaf and root transcriptome under each stress scenario revealed that most genes were differentially expressed in response to multiple stresses. The number of differentially expressed genes (DEGs) under stress was greater in leaf tissue, but roots exhibited a higher proportion of DEGs unique to individual stresses. Overall, the three water-related stresses had a more similar transcriptomic response to each other vs. low-nutrient stress, though this pattern was more pronounced in root tissue than in leaf tissue. In contrast with the results of our differential expression analysis, co-expression network analysis revealed that the response to each of the four stresses in our study were generally non-overlapping and there was little indication of a shared co-expression response despite the majority of DEGs being shared between multiple stresses. Importantly, PEG stress, which is often used to simulate drought stress in experimental settings, had little transcriptomic resemblance to true water limitation (i.e., dry-down) in our study calling into question its utility as a means for simulating drought.

scholarly journals Whole transcriptome approach to evaluate the effect of aluminium hydroxide in ovine encephalon

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Endika Varela-Martínez ◽  
Martin Bilbao-Arribas ◽  
Naiara Abendaño ◽  
Javier Asín ◽  
Marta Pérez ◽  
...  
Keyword(s):  
Aluminium Hydroxide ◽  
Neurological Diseases ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Mitochondrial Energy Metabolism ◽  
Differentially Expressed Mirnas ◽  
The Central Nervous System ◽  
Non Coding Rnas ◽  
Whole Transcriptome

Abstract Aluminium hydroxide adjuvants are crucial for livestock and human vaccines. Few studies have analysed their effect on the central nervous system in vivo. In this work, lambs received three different treatments of parallel subcutaneous inoculations during 16 months with aluminium-containing commercial vaccines, an equivalent dose of aluminium hydroxide or mock injections. Brain samples were sequenced by RNA-seq and miRNA-seq for the expression analysis of mRNAs, long non-coding RNAs and microRNAs and three expression comparisons were made. Although few differentially expressed genes were identified, some dysregulated genes by aluminium hydroxide alone were linked to neurological functions, the lncRNA TUNA among them, or were enriched in mitochondrial energy metabolism related functions. In the same way, the miRNA expression was mainly disrupted by the adjuvant alone treatment. Some differentially expressed miRNAs had been previously linked to neurological diseases, oxidative stress and apoptosis. In brief, in this study aluminium hydroxide alone altered the transcriptome of the encephalon to a higher degree than commercial vaccines that present a milder effect. The expression changes in the animals inoculated with aluminium hydroxide suggest mitochondrial disfunction. Further research is needed to elucidate to which extent these changes could have pathological consequences.

scholarly journals Whole-transcriptome sequencing of knee joint cartilage from osteoarthritis patients

2019 ◽  
Vol 8 (7) ◽  
pp. 290-303 ◽  
Author(s):  
H. Li ◽  
H. H. Yang ◽  
Z. G. Sun ◽  
H. B. Tang ◽  
J. K. Min
Keyword(s):  
Knee Joint ◽  
Transcriptome Sequencing ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Noncoding Rnas ◽  
Differentially Expressed ◽  
Cartilage Tissue ◽  
Joint Cartilage ◽  
Whole Transcriptome Sequencing ◽  
Whole Transcriptome

Objectives The aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA). Methods The expression profiles of mRNAs, lncRNAs, and circRNAs in OA cartilage were assessed using whole-transcriptome sequencing. Bioinformatics analyses included prediction and reannotation of novel lncRNAs and circRNAs, their classification, and their placement into subgroups. Gene ontology and pathway analysis were performed to identify differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs). We focused on the overlap of DEGs and targets of DELs previously identified in seven high-throughput studies. The top ten DELs were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in articular chondrocytes, both in vitro and in vivo. Results In total, 739 mRNAs, 1152 lncRNAs, and 42 circRNAs were found to be differentially expressed in OA cartilage tissue. Among these, we identified 18 overlapping DEGs and targets of DELs, and the top ten DELs were screened by expression profile analysis as candidate OA-related genes. WISP2, ATF3, and CHI3L1 were significantly increased in both normal versus OA tissues and normal versus interleukin (IL)-1β-induced OA-like cell models, while ADAM12, PRELP, and ASPN were shown to be significantly decreased. Among the identified DELs, we observed higher expression of ENST00000453554 and MSTRG.99593.3, and lower expression of MSTRG.44186.2 and NONHSAT186094.1 in normal versus OA cells and tissues. Conclusion This study revealed expression patterns of coding and noncoding RNAs in OA cartilage, which added sets of genes and noncoding RNAs to the list of candidate diagnostic biomarkers and therapeutic agents for OA patients. Cite this article: H. Li, H. H. Yang, Z. G. Sun, H. B. Tang, J. K. Min. Whole-transcriptome sequencing of knee joint cartilage from osteoarthritis patients. Bone Joint Res 2019;8:290–303. DOI: 10.1302/2046-3758.87.BJR-2018-0297.R1.

scholarly journals The Transcriptomic Response of the Murine Thyroid Gland to Iodide Overload and the Role of the Nrf2 Antioxidant System

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 884 ◽  
Author(s):  
Dionysios V. Chartoumpekis ◽  
Panos G. Ziros ◽  
Ilias Georgakopoulos-Soares ◽  
Adam A. T. Smith ◽  
Ana Claudia Marques ◽  
...  
Keyword(s):  
Transcriptional Response ◽  
Differentially Expressed ◽  
Graves Disease ◽  
Messenger Rnas ◽  
Follicular Cells ◽  
Transcriptomic Response ◽  
Nrf2 Pathway ◽  
Hormone Synthesis ◽  
Excess Iodide

Background: Thyroid follicular cells have physiologically high levels of reactive oxygen species because oxidation of iodide is essential for the iodination of thyroglobulin (Tg) during thyroid hormone synthesis. Thyroid follicles (the functional units of the thyroid) also utilize incompletely understood autoregulatory mechanisms to defend against exposure to excess iodide. To date, no transcriptomic studies have investigated these phenomena in vivo. Nuclear erythroid factor 2 like 2 (Nrf2 or Nfe2l2) is a transcription factor that regulates the expression of numerous antioxidant and other cytoprotective genes. We showed previously that the Nrf2 pathway regulates the antioxidant defense of follicular cells, as well as Tg transcription and Tg iodination. We, thus, hypothesized that Nrf2 might be involved in the transcriptional response to iodide overload. Methods: C57BL6/J wild-type (WT) or Nrf2 knockout (KO) male mice were administered regular water or water supplemented with 0.05% sodium iodide for seven days. RNA from their thyroids was prepared for next-generation RNA sequencing (RNA-Seq). Gene expression changes were assessed and pathway analyses were performed on the sets of differentially expressed genes. Results: Analysis of differentially expressed messenger RNAs (mRNAs) indicated that iodide overload upregulates inflammatory-, immune-, fibrosis- and oxidative stress-related pathways, including the Nrf2 pathway. Nrf2 KO mice showed a more pronounced inflammatory–autoimmune transcriptional response to iodide than WT mice. Compared to previously published datasets, the response patterns observed in WT mice had strong similarities with the patterns typical of Graves’ disease and papillary thyroid carcinoma (PTC). Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) also responded to iodide overload, with the latter targeting mRNAs that participate mainly in inflammation pathways. Conclusions: Iodide overload induces the Nrf2 cytoprotective response and upregulates inflammatory, immune, and fibrosis pathways similar to autoimmune hyperthyroidism (Graves’ disease) and PTC.

scholarly journals Comparative Transcriptomic Response of Two Pinus Species to Infection with the Pine Wood Nematode Bursaphelenchus xylophilus

Forests ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 204
Author(s):  
Gaspar ◽  
Trindade ◽  
Usié ◽  
Meireles ◽  
Fortes ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Transcriptional Profiling ◽  
Pine Wilt Disease ◽  
Bursaphelenchus Xylophilus ◽  
Differentially Expressed ◽  
Pine Wood Nematode ◽  
Transcriptomic Response ◽  
Pine Wood ◽  
Potential Impact ◽  
Pinus Spp

Pine wilt disease (PWD) caused by pine wood nematode (PWN), Bursaphelenchus xylophilus, is a serious threat to global forest populations of conifers, in particular Pinus spp. Recently, the presence of PWN was reported in dead Yunnan pine (Pinus yunnanensis) trees under natural conditions. To further understand the potential impact caused by PWN in Yunnan pine populations, a transcriptional profiling analysis was performed over different time points (0 hours (h), 6 h, 24 h, 48 h, and 7 days) after PWN inoculation. A total of 9961 differentially expressed genes were identified after inoculation, which suggested a dynamic response against the pathogen, with a more intense pattern at 48 h after inoculation. The results also highlighted a set of biological mechanisms triggered after inoculation that provide valuable information regarding the response of Yunnan pine to PWN infection. When compared with maritime pine (Pinus pinaster), the Yunnan pine response was less complex and involved a smaller number of differentially expressed genes, which may be associated with the increased degree of resistance to PWN displayed by Yunnan pine. These results revealed different strategies to cope with PWN infection by these two pine species, which display contrasting degrees of susceptibility, especially in the timely perception of the infection and response magnitude.

scholarly journals Comprehensive Evaluation of White Matter Damage and Neuron Death and Whole-Transcriptome Analysis of Rats With Chronic Cerebral Hypoperfusion

2019 ◽  
Vol 13 ◽  
Author(s):  
Wenxian Li ◽  
Di Wei ◽  
Jianye Liang ◽  
Xiaomei Xie ◽  
Kangping Song ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Neuronal Death ◽  
Chronic Cerebral Hypoperfusion ◽  
Differentially Expressed ◽  
Cerebral Hypoperfusion ◽  
Neuron Death ◽  
White Matter Damage ◽  
Morris Water Maze Task ◽  
Whole Transcriptome

Background/AimsChronic cerebral hypoperfusion (CCH) is induced by chronic deficit of brain perfusion, contributes to a persistent or progressive cognitive dysfunction, which is characterized by diverse neuropathological manifestations. There are currently no effective medications available. White matter damage (WMD) and cortical neuron death may be caused by CCH, which are related to cognitive impairment, while the underlying molecular mechanisms remain unclear. In the study, a database of the transcriptome level was built to determine potential biomarkers in cortex of CCH.MethodsCCH was induced in male Sprague-Dawley rats by permanent occlusion of the bilateral common carotid arteries. Rats were randomly divided into three groups: Sham-operated group (n = 24), the 4th and 8th week of CCH groups (total = 56, n = 28 for each group). Cognitive function was evaluated using the Morris water maze task. WMD and neuron damage were detected using diffusion tensor imaging and histological analysis, respectively. Western blotting analysis of various markers was used to examine neuronal death. Whole-transcriptome microarray was performed to assess mRNA, circRNA, and lncRNA expression profiles at 4th and 8th weeks after CCH. Diversified bioinformatic tools were performed to analyze and predict the key biological processes and signaling pathways of differentially expressed RNAs and co-expressed potential target genes. Co-expression networks of mRNA–circRNA–miRNA and lncRNA–mRNA were constructed.ResultsCompared to the sham group, cognitive impairment, disintegration of white matter, blood-brain barrier damage and neuron death were induced by CCH. Neuron death including apoptosis and necroptosis might occur in the cortex of CCH. We constructed the regulatory networks of whole-transcriptomic including differentially expressed mRNAs, circRNAs, and lncRNAs, and related biological functions and pathways involved in neurological disease, cell death and survival, energy and metabolism, et al. Our results also indicated that Cyr61 mRNA may play a role in the CCH-related cortical neuronal death.ConclusionWMD and cortical neuronal death are worthy of attention in the pathogenesis of CCH. Additionally, the present results provide potential evidence at the whole-transcription level for CCH, offering candidate biomarkers and therapeutic targets.

scholarly journals Bovine milk somatic cell transcriptomic response to Staphylococcus aureus is dependent on strain genotype

2021 ◽  
Author(s):  
Dagmara Niedziela ◽  
Paul Cormican ◽  
Gilles Foucras ◽  
Finola Leonard ◽  
Orla Keane
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Somatic Cell ◽  
Post Infection ◽  
Molecular Mechanisms ◽  
Clinical Signs ◽  
Differentially Expressed ◽  
Composition Analysis ◽  
Transcriptomic Response ◽  
M1 Macrophages

AbstractBackgroundMastitis is an economically important disease of dairy cows with Staphylococcus aureus a major cause worldwide. Challenge of Holstein-Friesian cows demonstrated that a strain belonging to Clonal Complex (CC)151 caused clinical mastitis, while a strain belonging to CC97 caused mild or subclinical mastitis. The aim of this study was to elucidate the molecular mechanisms of the host immune response utilising a transcriptomic approach. Milk somatic cells from cows infected with each strain of S. aureus at 0, 24, 48, 72 and 168 hours post-infection (hpi) were analysed for differentially expressed (DE) genes in response to each strain.ResultsIn response to MOK023 (CC97), 1278, 2278, 1986 and 1750 significant differentially expressed (DE) genes were found at 24, 48, 72 and 168 hpi, respectively, while 2293, 1979, 1428 and 1544 significant DE genes were found in response to MOK124 (CC151) at those time points. Genes involved in milk production (CSN1, CSN10, CSN1S2, CSN2, a-LACTA and PRLR) were downregulated in response to both strains, with a more pronounced decrease in the MOK124 group. Immune response pathways such as NF-κB and TNF signalling were overrepresented in response to both strains at 24 hpi. These immune pathways continued to be overrepresented in the MOK023 group at 48 and 72 hpi, while the Hippo signalling, extracellular matrix interaction (ECM) and tight junction pathways were overrepresented in the MOK124 group between 48 and 168 hpi. Cellular composition analysis demonstrated that a neutrophil response was predominant in response to MOK124, while M1 macrophages were the main milk cell type post-infection in the MOK023 group.ConclusionsA switch from immune response pathways to pathways involved in maintaining the integrity of the epithelial cell layer was observed in the MOK124 group from 48 hpi, which coincided with the occurrence of clinical signs in the infected animals. The higher proportion of M1 macrophages in the MOK023 group and lack of substantial neutrophil recruitment in response to MOK023 may indicate immune evasion by this strain. The results of this study highlight that the somatic cell transcriptomic response to S. aureus is dependent on the genotype of the infecting strain.

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