Rough virulent strain of Brucella ovis induces pro- and anti-inflammatory cytokines in reproductive tissues in experimentally infected rams

Antunes, João Marcelo Azevedo de Paula; Allendorf, Susan Dora; Appolinário, Camila Michele; Cagnini, Didier Quevedo; Figueiredo, Paula Ripamonte; Júnior, José Buratini; Vicente, Joaquín; Kocan, Katherine M.; Fuente, José de la; Megid, Jane

doi:10.1016/j.vetmic.2012.07.024

Cited by 14 publications

(4 citation statements)

References 20 publications

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“…These results are in accordance with Galindo et al [7] and Antunes et al [5], who reported that B. ovis induces downregulation of gene expression in order to supress the inflammatory host defenses infected rams. The inflammatory response induced by B. ovis represents an attempt to evade the immune response and suppress the host immune response [5,6]. In Table 2, the IPA tools through the canonical pathways emphasized an immune response associated with chronic of B. ovis infection.…”

Section: Chronic Phase Of Infection I (120 Dpc)supporting

confidence: 92%

“…In rams at 30 dpi with B. ovis in the acute phase of infection, the host immune response was notable with an up-regulation of several cytokines in reproductive tissues. During the development of infection, cytokine gene expression levels decreased, providing evidence of immunosuppression and immune evasion which favoured persistence of chronic B. ovis infection [5,6]. Previous microarray studies of gene expression patterns were done up to 60 dpi in rams experimentally-infected with B. ovis using buffy coat cells [7], and the use of heterologous array hybridization (screening for gene expression in one species using a microarray developed for another species) was also done [7,8].…”

Section: Introductionmentioning

confidence: 99%

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Microarray Analysis of Gene Expression in Rams Experimentally-Infected with the Virulent Strain of Brucella ovis

Antunes¹,

Allendorf²

2015

J Biotechnol Biomater

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Microarray analysis of gene expression profiles of total mRNA was studied in rams experimentally-infected with the virulent strain of Brucella ovis (B. ovis). The tissues studied included reproductive organs (epididymus, testicles, ampolae, vesicular glands, bulbourethral glands) and a pool of lymph nodes (inguinal and scrotal). The microarray analysis of each tissue was done at three time points: acute infection (60 days post infection [dpi]), chronic infection phase I (120 dpi), and chronic infection phase II (240 dpi). The gene expression profiles associated to B. ovis infection were determined using the Affymetrix Bovine Genome Array and expression levels of infected and uninfected rams (control group, 0 dpi) were compared. Of the 23,000 genes analyzed in the microarrays, 139 during acute phase of infection, 930 during the chronic phase I and 744 genes from the chronic phase II were identified as Differentially Expressed Genes (DEGs). Thirty known genes and fourteen unknown genes were expressed during the three phases of infection in all tissues. The biological functions of these genes included immune cell trafficking, immunological disease, infectious disease, inflammatory disease, inflammatory response and cellular movement, and significant differences were observed at the three phases of infection and in all infected tissues. For the first analysis, 8 genes in common during the three time points and to all infected tissues were chosen for the microarray validation. Acute phase of infection supported the relevance of the ataxia telangiectasia-mutated ATMIN (ATM interactor) gene. RCHY1 (ring finger and CHY zinc finger domain containing 1), ANKFY1 (ankyrin repeat and FYVE domain containing 1) and EFEMP1 (EGF-containing fibulin-like extracellular matrix protein 1) were also highlighted by the analysis during chronic phase I of infection. ZRAB2 (Zinc finger, RAN-binding domain containing 2) was validated at chronic phase II. This study represents the first analysis of microarray gene expression in different tissues of rams infected with of B. ovis at various times during infection and many of the genes identified require further study. These results expand the knowledge of the pathogenesis of this B. ovis strain infection in rams and suggest new genes and pathways for further investigation.

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Section: Chronic Phase Of Infection I (120 Dpc)supporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Microarray Analysis of Gene Expression in Rams Experimentally-Infected with the Virulent Strain of Brucella ovis

Antunes¹,

Allendorf²

2015

J Biotechnol Biomater

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“…The latter study concluded that LPS stimulation alters the expression of genes encoding epigenetic enzyme in bovine PBMC [16]. Real-time quantitative RT-PCR is the method commonly used for cytokine gene expression in tissues and has been used in sheep [72,87-89]. The qRT-PCR allows for an exponential amplification of the gene of interest; therefore, overcoming the sensitivity problems usually encountered with gene expression studies [72].…”

Section: Acute Phase Proteinsmentioning

confidence: 99%

Proteogenomics of selective susceptibility to endotoxin using circulating acute phase biomarkers and bioassay development in sheep: a review

Chemonges

Tung

2014

Proteome Sci

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Scientists have injected endotoxin into animals to investigate and understand various pathologies and novel therapies for several decades. Recent observations have shown that there is selective susceptibility to Escherichia coli lipopolysaccharide (LPS) endotoxin in sheep, despite having similar breed characteristics. The reason behind this difference is unknown, and has prompted studies aiming to explain the variation by proteogenomic characterisation of circulating acute phase biomarkers. It is hypothesised that genetic trait, biochemical, immunological and inflammation marker patterns contribute in defining and predicting mammalian response to LPS. This review discusses the effects of endotoxin and host responses, genetic basis of innate defences, activation of the acute phase response (APR) following experimental LPS challenge, and the current approaches employed in detecting novel biomarkers including acute phase proteins (APP) and micro-ribonucleic acids (miRNAs) in serum or plasma. miRNAs are novel targets for elucidating molecular mechanisms of disease because of their differential expression during pathological, and in healthy states. Changes in miRNA profiles during a disease challenge may be reflected in plasma. Studies show that gel-based two-dimensional electrophoresis (2-DE) coupled with either matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) or liquid chromatography–mass spectrometry (LC-MS/MS) are currently the most used methods for proteome characterisation. Further evidence suggests that proteomic investigations are preferentially shifting from 2-DE to non-gel based LC-MS/MS coupled with data extraction by sequential window acquisition of all theoretical fragment-ion spectra (SWATH) approaches that are able to identify a wider range of proteins. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and most recently proteomic methods have been used to quantify low abundance proteins such as cytokines. qRT-PCR and next generation sequencing (NGS) are used for the characterisation of miRNA. Proteogenomic approaches for detecting APP and novel miRNA profiling are essential in understanding the selective resistance to endotoxin in sheep. The results of these methods could help in understanding similar pathology in humans. It might also be helpful in the development of physiological and diagnostic screening assays for determining experimental inclusion and endpoints, and in clinical trials in future.

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“…Brucella induz apenas uma resposta inflamatória moderada que resulta provavelmente da evasão e supressão da resposta imune do hospedeiro susceptível (XAVIER et al, 2010;ANTUNES et al, 2013). Neste trabalho de revisão serão apresentados os mecanismos utilizados pela B. ovis, para invadir o hospedeiro e para proteger-se de sua resposta imune (Figura 1).…”

Section: Recentes Avanços Demonstraram Que O Gênerounclassified

Brucella ovis: invasão, tráfego, fatores de virulência e resposta imune

Antunes¹,

Megid²

2013

Sem. Ci. Agr.

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ResumoA brucelose permanece como problema econômico em animais e de saúde pública. Em todo o mundo a brucelose ovina ocasionada pela Brucella ovis é considerada uma das principais causas de infertilidade em ovinos. Os fatores responsáveis pela persistência do agente não são conhecidos, bem como os mecanismos imunes envolvidos na defesa e eventualmente na persistência do agente. Brucella spp. induz resposta inflamatória moderada. A natureza intracelular do agente estimula resposta imune celular do tipo linfócito T helper 1. Os estudos de patogenia da brucelose ovina são escassos. Recentes avanços demonstraram que a resposta inflamatória moderada induzida pelas brucelas representam provavelmente o resultado de tentativa de escape da resposta imune e supressão da resposta imune hospedeira. Foram revisados os mecanismos descritos pelas brucelas e pela Brucella ovis para penetração no hospedeiro, escape da resposta imune, bem como a resposta imunológica gerada pela infecção. Palavras-chave: Brucelose, patogenia, imunopatologia, Brucella ovis AbstractBrucellosis remains an economic problem in animals and public health. Worldwide ovine brucellosis caused by Brucella ovis is considered a major cause of infertility in sheep. The factors responsible for persistence of the agent are not known, as well as the mechanisms involved in immune defense and possibly the persistence of the agent. Brucella spp. induces moderate inflammatory response. The nature of the intracellular agent stimulates immune response of the type 1 helper T lymphocytes. Studies of the pathogenesis of ovine brucellosis are scarce. Recent developments have shown that the inflammatory response induced by moderate brucelas represent probably the result of an attempt to escape the immune response and suppression of host immune response. Were reviewed by the mechanisms described by brucelas and Brucella ovis for penetration into the host, escape of the immune response and the immune response generated by the infection.

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Rough virulent strain of Brucella ovis induces pro- and anti-inflammatory cytokines in reproductive tissues in experimentally infected rams

Cited by 14 publications

References 20 publications

Microarray Analysis of Gene Expression in Rams Experimentally-Infected with the Virulent Strain of Brucella ovis

Microarray Analysis of Gene Expression in Rams Experimentally-Infected with the Virulent Strain of Brucella ovis

Proteogenomics of selective susceptibility to endotoxin using circulating acute phase biomarkers and bioassay development in sheep: a review

Brucella ovis: invasão, tráfego, fatores de virulência e resposta imune

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