Dataset Information

Global Gene Networks in 3D4/31 Porcine Alveolar Macrophages Treated with Antigenic Epitopes of Actinobacillus pleuropneumoniae ApxIA, IIA, and IVA.

ABSTRACT: Actinobacillus pleuropneumoniae (App) is the causative agent of porcine pleuropneumonia. Although App produces several virulence factors, Apx toxins, the primary App virulence factors, have been the focus of numerous studies. However, the host response against the Apx toxins has not been elucidated at the transcriptomic level. Therefore, in this study, we examined the response of an immortalized porcine alveolar macrophage cell line (IPAM 3D4/31) to four antigenic epitopes of the App exotoxins, ApxIA, IIA and IVA. The antigenic epitopes of the Apx toxins (ApxIA Ct, ApxIIA Nt, ApxIVA C1 and ApxIV C2) were determined by an in-silico antigenicity prediction analysis. Gene expression in IPAMs was analyzed by RNA-Seq after treatment with the four proteins for 24?h. A total of 15,269 DEGs were observed to be associated with cellular and metabolic processes in the GO category Biological Process and nuclear receptors and apoptosis signaling in IPA analyses. These DEGs were also related to M2 macrophage polarization and apoptosis in IPAMs. These host transcriptional analyses present novel global gene networks of the host response to treatment with Apx toxins.

SUBMITTER: Kim S

PROVIDER: S-EPMC6437162 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Global Gene Networks in 3D4/31 Porcine Alveolar Macrophages Treated with Antigenic Epitopes of Actinobacillus pleuropneumoniae ApxIA, IIA, and IVA.

Kim Suji S Oh Myung Whan MW Bin Park Woo W Yoo Han Sang HS

Scientific reports 20190327 1

Actinobacillus pleuropneumoniae (App) is the causative agent of porcine pleuropneumonia. Although App produces several virulence factors, Apx toxins, the primary App virulence factors, have been the focus of numerous studies. However, the host response against the Apx toxins has not been elucidated at the transcriptomic level. Therefore, in this study, we examined the response of an immortalized porcine alveolar macrophage cell line (IPAM 3D4/31) to four antigenic epitopes of the App exotoxins, ...[more]

PMID: 30918280

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Project description:Outer membrane vesicles (OMVs) are spontaneously released by Gram-negative bacteria, including Actinobacillus pleuropneumoniae, which causes contagious pleuropneumonia in pigs and leads to considerable economic losses in the swine industry worldwide. A. pleuropneumoniae OMVs have previously been demonstrated to contain Apx toxins and proteases, as well as antigenic proteins. Nevertheless, comprehensive characterizations of their contents and interactions with host immune cells have not been made. Understanding the protein compositions and immunomodulating ability of A. pleuropneumoniae OMVs could help illuminate their biological functions and facilitate the development of OMV-based applications. In the current investigation, we comprehensively characterized the proteome of native A. pleuropneumoniae OMVs. Moreover, we qualitatively and quantitatively compared the OMV proteomes of a wild-type strain and three mutant strains, in which relevant genes were disrupted to increase OMV production and/or produce OMVs devoid of superantigen PalA. Furthermore, the interaction between A. pleuropneumoniae OMVs and porcine alveolar macrophages was also characterized. Our results indicate that native OMVs spontaneously released by A. pleuropneumoniae MIDG2331 appeared to dampen the innate immune responses by porcine alveolar macrophages stimulated by either inactivated or live parent cells. The findings suggest that OMVs may play a role in manipulating the porcine defense during the initial phases of the A. pleuropneumoniae infection. IMPORTANCE Owing to their built-in adjuvanticity and antigenicity, bacterial outer membrane vesicles (OMVs) are gaining increasing attention as potential vaccines for both human and animal use. OMVs released by Actinobacillus pleuropneumoniae, an important respiratory pathogen in pigs, have also been investigated for vaccine development. Our previous studies have shown that A. pleuropneumoniae secretes OMVs containing multiple immunogenic proteins. However, immunization of pigs with these vesicles was not able to relieve the pig lung lesions induced by the challenge with A. pleuropneumoniae, implying the elusive roles that A. pleuropneumoniae OMVs play in host-pathogen interaction. Here, we showed that A. pleuropneumoniae secretes OMVs whose yield and protein content can be altered by the deletion of the nlpI and palA genes. Furthermore, we demonstrate that A. pleuropneumoniae OMVs dampen the immune responses in porcine alveolar macrophages stimulated by A. pleuropneumoniae cells, suggesting a novel mechanism that A. pleuropneumoniae might use to evade host defense.

Dataset Information

Global Gene Networks in 3D4/31 Porcine Alveolar Macrophages Treated with Antigenic Epitopes of Actinobacillus pleuropneumoniae ApxIA, IIA, and IVA.

Publications

Global Gene Networks in 3D4/31 Porcine Alveolar Macrophages Treated with Antigenic Epitopes of Actinobacillus pleuropneumoniae ApxIA, IIA, and IVA.

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