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Whole Blood Transcriptome Analysis of Mycoplasma mycoides Subsp. mycoides-Infected Cattle Confirms Immunosuppression but Does Not Reflect Local Inflammation.

Rodrigues V, Holzmuller P, Puech C, Wesonga H, Thiaucourt F, Manso-Silván L - PLoS ONE (2015)

Bottom Line: These affected functions were consistent with the results of previous in vitro immunological studies.However, microarray and qPCR validation results did not highlight pro-inflammatory molecules (such as TNFα, TLR2, IL-12B and IL-6), whereas inflammation is one of the most characteristic traits of acute CBPP.This global gene expression pattern may be considered as the result, in blood, of the local pulmonary response and the systemic events occurring during acute CBPP.

View Article: PubMed Central - PubMed

Affiliation: CIRAD, UMR15 CMAEE, F-34398 Montpellier, France; INRA, UMR1309 CMAEE, F-34398 Montpellier, France.

ABSTRACT
Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides (Mmm), is a severe respiratory disease of cattle responsible for major economic losses in sub-Saharan Africa. Disease control relies mainly on the use of empirically attenuated vaccines that provide limited protection. Thus, understanding the virulence mechanisms used by Mmm as well as the role of the host immune system in disease development, persistence, and control is a prerequisite for the development of new, rationally designed control strategies. The aim of this study was to assess the use of whole blood transcriptome analysis to study cattle-Mmm interactions, starting by the characterization of the bovine response to Mmm infection during the acute form of the disease. For that purpose, we compared the transcriptome profile of whole blood from six cattle, before challenge by contact with Mmm-infected animals and at the appearance of first clinical signs, using a bovine microarray. Functional analysis revealed that 680 annotated genes were differentially expressed, with an overwhelming majority of down-regulated genes characterizing an immunosuppression. The main bio-functions affected were "organismal survival", "cellular development, morphology and functions" and "cell-to cell signaling and interactions". These affected functions were consistent with the results of previous in vitro immunological studies. However, microarray and qPCR validation results did not highlight pro-inflammatory molecules (such as TNFα, TLR2, IL-12B and IL-6), whereas inflammation is one of the most characteristic traits of acute CBPP. This global gene expression pattern may be considered as the result, in blood, of the local pulmonary response and the systemic events occurring during acute CBPP. Nevertheless, to understand the immune events occurring during disease, detailed analyses on the different immune cell subpopulations, either in vivo, at the local site, or in vitro, will be required. Whole blood transcriptome analysis remains an interesting approach for the identification of bio-signatures correlating to recovery and protection, which should facilitate the evaluation and validation of novel vaccine formulations.

No MeSH data available.


Related in: MedlinePlus

Top functions related to immune response differentially expressed in whole blood of Mmm-infected cattle.The ten most modulated top functions related to immune response were categorized by Ingenuity Pathway Analysis software according to p-values and z-scores. The number of differentially expressed genes in each top function is given.
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pone.0139678.g003: Top functions related to immune response differentially expressed in whole blood of Mmm-infected cattle.The ten most modulated top functions related to immune response were categorized by Ingenuity Pathway Analysis software according to p-values and z-scores. The number of differentially expressed genes in each top function is given.

Mentions: To better understand the biological significance of the modulated genes, we performed bio-function analysis using IPA software. The 1,115 previously identified entities were separated into 786 mapped entities and 329 unmapped entities. A deduplication exercise on mapped entities resulted in a final list of 680 identified genes (S1 Table) of which 544 genes (i.e. 80%) were down-regulated in infected cattle. The 680 differentially-expressed genes were categorized and subcategorized according to their p-values and z-scores, revealing 10 most modulated top functions related to immune response in the infected group (Fig 3). These 10 top functions were subcategorized into bio-functions by IPA (Table 2).


Whole Blood Transcriptome Analysis of Mycoplasma mycoides Subsp. mycoides-Infected Cattle Confirms Immunosuppression but Does Not Reflect Local Inflammation.

Rodrigues V, Holzmuller P, Puech C, Wesonga H, Thiaucourt F, Manso-Silván L - PLoS ONE (2015)

Top functions related to immune response differentially expressed in whole blood of Mmm-infected cattle.The ten most modulated top functions related to immune response were categorized by Ingenuity Pathway Analysis software according to p-values and z-scores. The number of differentially expressed genes in each top function is given.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4592004&req=5

pone.0139678.g003: Top functions related to immune response differentially expressed in whole blood of Mmm-infected cattle.The ten most modulated top functions related to immune response were categorized by Ingenuity Pathway Analysis software according to p-values and z-scores. The number of differentially expressed genes in each top function is given.
Mentions: To better understand the biological significance of the modulated genes, we performed bio-function analysis using IPA software. The 1,115 previously identified entities were separated into 786 mapped entities and 329 unmapped entities. A deduplication exercise on mapped entities resulted in a final list of 680 identified genes (S1 Table) of which 544 genes (i.e. 80%) were down-regulated in infected cattle. The 680 differentially-expressed genes were categorized and subcategorized according to their p-values and z-scores, revealing 10 most modulated top functions related to immune response in the infected group (Fig 3). These 10 top functions were subcategorized into bio-functions by IPA (Table 2).

Bottom Line: These affected functions were consistent with the results of previous in vitro immunological studies.However, microarray and qPCR validation results did not highlight pro-inflammatory molecules (such as TNFα, TLR2, IL-12B and IL-6), whereas inflammation is one of the most characteristic traits of acute CBPP.This global gene expression pattern may be considered as the result, in blood, of the local pulmonary response and the systemic events occurring during acute CBPP.

View Article: PubMed Central - PubMed

Affiliation: CIRAD, UMR15 CMAEE, F-34398 Montpellier, France; INRA, UMR1309 CMAEE, F-34398 Montpellier, France.

ABSTRACT
Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides (Mmm), is a severe respiratory disease of cattle responsible for major economic losses in sub-Saharan Africa. Disease control relies mainly on the use of empirically attenuated vaccines that provide limited protection. Thus, understanding the virulence mechanisms used by Mmm as well as the role of the host immune system in disease development, persistence, and control is a prerequisite for the development of new, rationally designed control strategies. The aim of this study was to assess the use of whole blood transcriptome analysis to study cattle-Mmm interactions, starting by the characterization of the bovine response to Mmm infection during the acute form of the disease. For that purpose, we compared the transcriptome profile of whole blood from six cattle, before challenge by contact with Mmm-infected animals and at the appearance of first clinical signs, using a bovine microarray. Functional analysis revealed that 680 annotated genes were differentially expressed, with an overwhelming majority of down-regulated genes characterizing an immunosuppression. The main bio-functions affected were "organismal survival", "cellular development, morphology and functions" and "cell-to cell signaling and interactions". These affected functions were consistent with the results of previous in vitro immunological studies. However, microarray and qPCR validation results did not highlight pro-inflammatory molecules (such as TNFα, TLR2, IL-12B and IL-6), whereas inflammation is one of the most characteristic traits of acute CBPP. This global gene expression pattern may be considered as the result, in blood, of the local pulmonary response and the systemic events occurring during acute CBPP. Nevertheless, to understand the immune events occurring during disease, detailed analyses on the different immune cell subpopulations, either in vivo, at the local site, or in vitro, will be required. Whole blood transcriptome analysis remains an interesting approach for the identification of bio-signatures correlating to recovery and protection, which should facilitate the evaluation and validation of novel vaccine formulations.

No MeSH data available.


Related in: MedlinePlus