Differential Homing Receptor Profiles of Lymphocytes Induced by Attenuated versus Live <i>Plasmodium falciparum</i> Sporozoites
The onset of an adaptive immune response provides the signals required for differentiation of antigen-specific lymphocytes into effector cells and imprinting of these cells for re-circulation to the most appropriate anatomical site (i.e., homing). Lymphocyte homing is governed by the expression of t...
| Autores principales: | , , , |
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| Formato: | Artículo |
| Lenguaje: | English |
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MDPI AG
2022-10-01
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| Colección: | Vaccines |
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| Acceso en línea: | https://www.mdpi.com/2076-393X/10/10/1768 |
| _version_ | 1827647727508389888 |
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| author | Marie Mura Tanmaya Atre Tatyana Savransky Elke S. Bergmann-Leitner |
| author_facet | Marie Mura Tanmaya Atre Tatyana Savransky Elke S. Bergmann-Leitner |
| author_sort | Marie Mura |
| collection | DOAJ |
| description | The onset of an adaptive immune response provides the signals required for differentiation of antigen-specific lymphocytes into effector cells and imprinting of these cells for re-circulation to the most appropriate anatomical site (i.e., homing). Lymphocyte homing is governed by the expression of tissue-specific lymphocyte homing receptors that bind to unique tissue-specific ligands on endothelial cells. In this study, a whole-parasite malaria vaccine (radiation-attenuated sporozoites (RAS)) was used as a model system to establish homing receptor signatures induced by the parasite delivered through mosquito bite to provide a benchmark of desirable homing receptors for malaria vaccine developers. This immunization regimen resulted in the priming of antigen-specific B cells and CD8<sup>+</sup> T cells for homing primarily to the skin and T/B cell compartments of secondary lymphoid organs. Infection with live sporozoites, however, triggers the upregulation of homing receptor for the liver and the skin, demonstrating that there is a difference in the signal provided by attenuated vs. live sporozoites. This is the first report on imprinting of homing routes by <i>Plasmodium</i> sporozoites and, surprisingly, it also points to additional, yet to be identified, signals provided by live parasites that prime lymphocytes for homing to the liver. The data also demonstrate the utility of this method for assessing the potential of vaccine formulations to direct antigen-specific lymphocytes to the most relevant anatomical site, thus potentially impacting vaccine efficacy. |
| first_indexed | 2024-03-09T19:23:36Z |
| format | Article |
| id | doaj.art-08d84ec0fef043b79d0e7c0e83e9f8c2 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T19:23:36Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-08d84ec0fef043b79d0e7c0e83e9f8c22023-11-24T03:05:46ZengMDPI AGVaccines2076-393X2022-10-011010176810.3390/vaccines10101768Differential Homing Receptor Profiles of Lymphocytes Induced by Attenuated versus Live <i>Plasmodium falciparum</i> SporozoitesMarie Mura0Tanmaya Atre1Tatyana Savransky2Elke S. Bergmann-Leitner3Immunology Core, Biologics Research & Development, WRAIR—Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAImmunology Core, Biologics Research & Development, WRAIR—Walter Reed Army Institute of Research, Silver Spring, MD 20910, USADivision of Entomology, WRAIR—Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAImmunology Core, Biologics Research & Development, WRAIR—Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAThe onset of an adaptive immune response provides the signals required for differentiation of antigen-specific lymphocytes into effector cells and imprinting of these cells for re-circulation to the most appropriate anatomical site (i.e., homing). Lymphocyte homing is governed by the expression of tissue-specific lymphocyte homing receptors that bind to unique tissue-specific ligands on endothelial cells. In this study, a whole-parasite malaria vaccine (radiation-attenuated sporozoites (RAS)) was used as a model system to establish homing receptor signatures induced by the parasite delivered through mosquito bite to provide a benchmark of desirable homing receptors for malaria vaccine developers. This immunization regimen resulted in the priming of antigen-specific B cells and CD8<sup>+</sup> T cells for homing primarily to the skin and T/B cell compartments of secondary lymphoid organs. Infection with live sporozoites, however, triggers the upregulation of homing receptor for the liver and the skin, demonstrating that there is a difference in the signal provided by attenuated vs. live sporozoites. This is the first report on imprinting of homing routes by <i>Plasmodium</i> sporozoites and, surprisingly, it also points to additional, yet to be identified, signals provided by live parasites that prime lymphocytes for homing to the liver. The data also demonstrate the utility of this method for assessing the potential of vaccine formulations to direct antigen-specific lymphocytes to the most relevant anatomical site, thus potentially impacting vaccine efficacy.https://www.mdpi.com/2076-393X/10/10/1768lymphocyte homingvaccinemalariaflow cytometryparasite<i>Plasmodium</i> |
| spellingShingle | Marie Mura Tanmaya Atre Tatyana Savransky Elke S. Bergmann-Leitner Differential Homing Receptor Profiles of Lymphocytes Induced by Attenuated versus Live <i>Plasmodium falciparum</i> Sporozoites Vaccines lymphocyte homing vaccine malaria flow cytometry parasite <i>Plasmodium</i> |
| title | Differential Homing Receptor Profiles of Lymphocytes Induced by Attenuated versus Live <i>Plasmodium falciparum</i> Sporozoites |
| title_full | Differential Homing Receptor Profiles of Lymphocytes Induced by Attenuated versus Live <i>Plasmodium falciparum</i> Sporozoites |
| title_fullStr | Differential Homing Receptor Profiles of Lymphocytes Induced by Attenuated versus Live <i>Plasmodium falciparum</i> Sporozoites |
| title_full_unstemmed | Differential Homing Receptor Profiles of Lymphocytes Induced by Attenuated versus Live <i>Plasmodium falciparum</i> Sporozoites |
| title_short | Differential Homing Receptor Profiles of Lymphocytes Induced by Attenuated versus Live <i>Plasmodium falciparum</i> Sporozoites |
| title_sort | differential homing receptor profiles of lymphocytes induced by attenuated versus live i plasmodium falciparum i sporozoites |
| topic | lymphocyte homing vaccine malaria flow cytometry parasite <i>Plasmodium</i> |
| url | https://www.mdpi.com/2076-393X/10/10/1768 |
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