Serum IgM Glycosylation Associated with Tuberculosis Infection in Mice
ABSTRACT Changes in serum glycans discriminate between disease statuses in cancer. A similar connection has not been established in the context of infectious diseases such as tuberculosis (TB). The inflammation arising from infection by Mycobacterium tuberculosis may affect host protein glycosylatio...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2019-04-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00684-18 |
| _version_ | 1818834824772714496 |
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| author | Tadahiro Kumagai Ainhoa Palacios Arturo Casadevall M. Jesús García Carlos Toro Michael Tiemeyer Rafael Prados-Rosales |
| author_facet | Tadahiro Kumagai Ainhoa Palacios Arturo Casadevall M. Jesús García Carlos Toro Michael Tiemeyer Rafael Prados-Rosales |
| author_sort | Tadahiro Kumagai |
| collection | DOAJ |
| description | ABSTRACT Changes in serum glycans discriminate between disease statuses in cancer. A similar connection has not been established in the context of infectious diseases such as tuberculosis (TB). The inflammation arising from infection by Mycobacterium tuberculosis may affect host protein glycosylation, thereby providing information about disease status in TB. A mouse model of infection was used to study glycoprotein N-glycosylation in serum. Following digestion of serum glycoproteins with peptide-N-glycosidase F (PNGase F), released glycans were permethylated and analyzed by multidimensional mass spectrometry (MS). Conditions included naive or Mycobacterium bovis BCG-vaccinated animals, which were either uninfected or infected with M. tuberculosis. MS results were validated by lectin blotting. We found that both glycoprotein fucosylation and sialylation were particularly sensitive to M. tuberculosis infection. We observed that M. tuberculosis infection elevates serum IgM levels and induces changes in glycosylation that could inform about the disease. IMPORTANCE We demonstrate that M. tuberculosis infection influenced host protein glycosylation in a mouse model. The mechanism by which infection modifies glycans in serum proteins is not understood. Investigation of the regulation of such modifications by M. tuberculosis opens a new field that could lead to the discovery of novel biomarkers. Validation of such findings in human samples will reveal the clinical relevance of these findings. |
| first_indexed | 2024-12-19T02:40:58Z |
| format | Article |
| id | doaj.art-1c6d8067a5e341608122edaf43ec763a |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-19T02:40:58Z |
| publishDate | 2019-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-1c6d8067a5e341608122edaf43ec763a2022-12-21T20:39:08ZengAmerican Society for MicrobiologymSphere2379-50422019-04-014210.1128/mSphere.00684-18Serum IgM Glycosylation Associated with Tuberculosis Infection in MiceTadahiro Kumagai0Ainhoa Palacios1Arturo Casadevall2M. Jesús García3Carlos Toro4Michael Tiemeyer5Rafael Prados-Rosales6Complex Carbohydrate Research Center, The University of Georgia, Athens, Georgia, USACIC bioGUNE, Derio, Bizkaia, SpainDepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USADepartment of Preventive Medicine, Public Health and Microbiology, Autonomous University of Madrid, Madrid, SpainService of Microbiology, Hospital Universitario La Paz, IdiPaz, Madrid, SpainComplex Carbohydrate Research Center, The University of Georgia, Athens, Georgia, USACIC bioGUNE, Derio, Bizkaia, SpainABSTRACT Changes in serum glycans discriminate between disease statuses in cancer. A similar connection has not been established in the context of infectious diseases such as tuberculosis (TB). The inflammation arising from infection by Mycobacterium tuberculosis may affect host protein glycosylation, thereby providing information about disease status in TB. A mouse model of infection was used to study glycoprotein N-glycosylation in serum. Following digestion of serum glycoproteins with peptide-N-glycosidase F (PNGase F), released glycans were permethylated and analyzed by multidimensional mass spectrometry (MS). Conditions included naive or Mycobacterium bovis BCG-vaccinated animals, which were either uninfected or infected with M. tuberculosis. MS results were validated by lectin blotting. We found that both glycoprotein fucosylation and sialylation were particularly sensitive to M. tuberculosis infection. We observed that M. tuberculosis infection elevates serum IgM levels and induces changes in glycosylation that could inform about the disease. IMPORTANCE We demonstrate that M. tuberculosis infection influenced host protein glycosylation in a mouse model. The mechanism by which infection modifies glycans in serum proteins is not understood. Investigation of the regulation of such modifications by M. tuberculosis opens a new field that could lead to the discovery of novel biomarkers. Validation of such findings in human samples will reveal the clinical relevance of these findings.https://journals.asm.org/doi/10.1128/mSphere.00684-18IgMMycobacterium tuberculosisfucosylationglycansimmunoglobulin Mmice |
| spellingShingle | Tadahiro Kumagai Ainhoa Palacios Arturo Casadevall M. Jesús García Carlos Toro Michael Tiemeyer Rafael Prados-Rosales Serum IgM Glycosylation Associated with Tuberculosis Infection in Mice mSphere IgM Mycobacterium tuberculosis fucosylation glycans immunoglobulin M mice |
| title | Serum IgM Glycosylation Associated with Tuberculosis Infection in Mice |
| title_full | Serum IgM Glycosylation Associated with Tuberculosis Infection in Mice |
| title_fullStr | Serum IgM Glycosylation Associated with Tuberculosis Infection in Mice |
| title_full_unstemmed | Serum IgM Glycosylation Associated with Tuberculosis Infection in Mice |
| title_short | Serum IgM Glycosylation Associated with Tuberculosis Infection in Mice |
| title_sort | serum igm glycosylation associated with tuberculosis infection in mice |
| topic | IgM Mycobacterium tuberculosis fucosylation glycans immunoglobulin M mice |
| url | https://journals.asm.org/doi/10.1128/mSphere.00684-18 |
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