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Expression profile of porcine scavenger receptor A and its role in bacterial phagocytosis by macrophages.

ABSTRACT: Expression of scavenger receptor A (SRA) in macrophages plays key role in macrophage mediated uptake of microbes. However, little is known about the role of porcine scavenger receptor A (pSRA) in phagocytic function of macrophages in swine species. In this study, polyclonal antibody against pSRA was generated by using recombinant proteins to study expression and function of pSRA. We report broad expression of pSRA in different tissues. In the lungs, pSRA is mainly expressed by alveolar macrophages. Blockade of class A scavenger receptor by fucoidan treatment demonstrates that pSRA has role in bacterial phagocytosis by macrophages. Furthermore, importance of SRA-mediated bacterial phagocytosis has been shown using CHO cell line expressing pSRA. In summary, these findings reveal that pSRA, which is predominantly expressed in alveolar macrophages is likely to be an important receptor mediating recognition and uptake of bacteria in pig lungs.

SUBMITTER: Xiang X

PROVIDER: S-EPMC7796722 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Expression profile of porcine scavenger receptor A and its role in bacterial phagocytosis by macrophages.

Xiang Xiao X Zhang Yanbing Y Li Qianqian Q Wei Jianchao J Liu Ke K Shao Donghua D Li Beibei B Olszewski Michal A MA Ma Zhiyong Z Qiu Yafeng Y

Developmental and comparative immunology 20191102

Expression of scavenger receptor A (SRA) in macrophages plays key role in macrophage mediated uptake of microbes. However, little is known about the role of porcine scavenger receptor A (pSRA) in phagocytic function of macrophages in swine species. In this study, polyclonal antibody against pSRA was generated by using recombinant proteins to study expression and function of pSRA. We report broad expression of pSRA in different tissues. In the lungs, pSRA is mainly expressed by alveolar macrophag ...[more]

PMID: 31689452

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Project description:BACKGROUND:Toxoplasma gondii is an apicomplexan protozoan parasite that can cause serious clinical illnesses in both humans and animals. microRNAs (miRNAs) are non-protein-coding RNAs that can regulate the expression of target genes. A previous study found that many miRNAs were differentially expressed after T. gondii infection and exert significant effects and revealed that both host survival and the virulence of different strains can be regulated by different miRNAs. Macrophages play an important role in T. gondii infection, but few studies have investigated the relationship between miRNAs and porcine alveolar macrophages infected with T. gondii. METHODS:Porcine alveolar macrophages (3D4-21) were infected with the RH (Type I) and Me49 (Type II) strains of T. gondii for 12 h and 24 h and then harvested. miRNA libraries were generated using the NEBNext® Multiplex Small RNA Library Prep Set for Illumina® (NEB, USA), and the miRNA expression levels were estimated based on transcripts per million reads (TPM). RESULTS:Our study generated six miRNA expression profiles from macrophages infected with RH and Me49 compared with the control groups. The comparison of the T. gondii-infected and uninfected samples identified 81 differentially expressed miRNAs, including 36 novel miRNAs and 45 mature miRNAs. The target genes of these differentially expressed miRNAs were predicted using miRanda software, and ssc-miR-127 and ssc-miR-143-3p were predicted to regulate nitric oxide synthase 1 (NOS1) and nitric oxide synthase 3 (NOS3), respectively, which play essential roles in synthesizing nitric oxide (NO) by oxidizing L-arginine. These genes were differentially expressed in both the RH- and Me49-infected groups. A KEGG enrichment analysis indicated that the predicted target genes were involved in multiple signaling pathways, including Fc?R-mediated phagocytosis, the AMPK signaling pathway, the mTOR signaling pathway, and the Fc?RI signaling pathway, all of which are indispensable for the normal functioning of porcine alveolar macrophages. CONCLUSIONS:Our results provide data on the miRNA profile of porcine alveolar macrophages infected with T. gondii. To our knowledge, this study provides the first demonstration of the relationship between miRNA and macrophages of swine origin. Understanding the functions of these regulated miRNAs will aid the investigation of T. gondii infectious diseases, and the differentially expressed miRNAs might be candidate drug targets for T. gondii infection in pigs.

Project description:The scavenger receptor MARCO is expressed in several subsets of naive tissue-resident macrophages and has been shown to participate in the recognition of various bacterial pathogens. However, the role of MARCO in antiviral defense is largely unexplored. Here, we investigated whether MARCO might be involved in the innate sensing of infection with adenovirus and recombinant adenoviral vectors by macrophages, which elicit vigorous immune responses in vivo Using cells derived from mice, we show that adenovirus infection is significantly more efficient in MARCO-positive alveolar macrophages (AMs) and in AM-like primary macrophage lines (Max Planck Institute cells) than in MARCO-negative bone marrow-derived macrophages. Using antibodies blocking ligand binding to MARCO, as well as gene-deficient and MARCO-transfected cells, we show that MARCO mediates the rapid adenovirus transduction of macrophages. By enhancing adenovirus infection, MARCO contributes to efficient innate virus recognition through the cytoplasmic DNA sensor cGAS. This leads to strong proinflammatory responses, including the production of interleukin-6 (IL-6), alpha/beta interferon, and mature IL-1α. These findings contribute to the understanding of viral pathogenesis in macrophages and may open new possibilities for the development of tools to influence the outcome of infection with adenovirus or adenovirus vectors.IMPORTANCE Macrophages play crucial roles in inflammation and defense against infection. Several macrophage subtypes have been identified with differing abilities to respond to infection with both natural adenoviruses and recombinant adenoviral vectors. Adenoviruses are important respiratory pathogens that elicit vigorous innate responses in vitro and in vivo The cell surface receptors mediating macrophage type-specific adenovirus sensing are largely unknown. The scavenger receptor MARCO is expressed on some subsets of naive tissue-resident macrophages, including lung alveolar macrophages. Its role in antiviral macrophage responses is largely unexplored. Here, we studied whether the differential expression of MARCO might contribute to the various susceptibilities of macrophage subtypes to adenovirus. We demonstrate that MARCO significantly enhances adenovirus infection and innate responses in macrophages. These results help to understand adenoviral pathogenesis and may open new possibilities to influence the outcome of infection with adenoviruses or adenovirus vectors.

Dataset Information

Expression profile of porcine scavenger receptor A and its role in bacterial phagocytosis by macrophages.

Publications

Expression profile of porcine scavenger receptor A and its role in bacterial phagocytosis by macrophages.

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