Group 2 Innate Lymphoid Cells (ILC2) Suppress Beneficial Type 1 Immune Responses During Pulmonary Cryptococcosis
Cryptococcus neoformans is an opportunistic fungal pathogen preferentially causing disease in immunocompromised individuals such as organ-transplant-recipients, patients receiving immunosuppressive medications or, in particular, individuals suffering from HIV infection. Numerous studies clearly indi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00209/full |
| _version_ | 1818037685937242112 |
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| author | Markus Kindermann Lisa Knipfer Stephanie Obermeyer Uwe Müller Gottfried Alber Christian Bogdan Christian Bogdan Ulrike Schleicher Ulrike Schleicher Markus F. Neurath Markus F. Neurath Stefan Wirtz Stefan Wirtz |
| author_facet | Markus Kindermann Lisa Knipfer Stephanie Obermeyer Uwe Müller Gottfried Alber Christian Bogdan Christian Bogdan Ulrike Schleicher Ulrike Schleicher Markus F. Neurath Markus F. Neurath Stefan Wirtz Stefan Wirtz |
| author_sort | Markus Kindermann |
| collection | DOAJ |
| description | Cryptococcus neoformans is an opportunistic fungal pathogen preferentially causing disease in immunocompromised individuals such as organ-transplant-recipients, patients receiving immunosuppressive medications or, in particular, individuals suffering from HIV infection. Numerous studies clearly indicated that the control of C. neoformans infections is strongly dependent on a prototypic type 1 immune response and classical macrophage activation, whereas type 2-biased immunity and alternative activation of macrophages has been rather implicated in disease progression and detrimental outcomes. However, little is known about regulatory pathways modulating and balancing immune responses during early phases of pulmonary cryptococcosis. Here, we analyzed the role of group 2 innate lymphoid cells (ILC2s) for the control of C. neoformans infection. Using an intranasal infection model with a highly virulent C. neoformans strain, we found that ILC2 numbers were strongly increased in C. neoformans-infected lungs along with induction of a type 2 response. Mice lacking ILC2s due to conditional deficiency of the transcription factor RAR-related orphan receptor alpha (Rora) displayed a massive downregulation of features of type 2 immunity as reflected by reduced levels of the type 2 signature cytokines IL-4, IL-5, and IL-13 at 14 days post-infection. Moreover, ILC2 deficiency was accompanied with increased type 1 immunity and classical macrophage activation, while the pulmonary numbers of eosinophils and alternatively activated macrophages were reduced in these mice. Importantly, this shift in pulmonary macrophage polarization in ILC2-deficient mice correlated with improved fungal control and prolonged survival of infected mice. Conversely, adoptive transfer of ILC2s was associated with a type 2 bias associated with less efficient anti-fungal immunity in lungs of recipient mice. Collectively, our date indicate a non-redundant role of ILC2 in orchestrating myeloid anti-cryptococcal immune responses toward a disease exacerbating phenotype. |
| first_indexed | 2024-12-10T07:30:47Z |
| format | Article |
| id | doaj.art-89e438a067154663a07bd2d067838e76 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T07:30:47Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-89e438a067154663a07bd2d067838e762022-12-22T01:57:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-02-011110.3389/fimmu.2020.00209500942Group 2 Innate Lymphoid Cells (ILC2) Suppress Beneficial Type 1 Immune Responses During Pulmonary CryptococcosisMarkus Kindermann0Lisa Knipfer1Stephanie Obermeyer2Uwe Müller3Gottfried Alber4Christian Bogdan5Christian Bogdan6Ulrike Schleicher7Ulrike Schleicher8Markus F. Neurath9Markus F. Neurath10Stefan Wirtz11Stefan Wirtz12Medizinische Klinik 1, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyMedizinische Klinik 1, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyMikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyCentre for Biotechnology and Biomedicine, Institute of Immunology, College of Veterinary Medicine, University of Leipzig, Leipzig, GermanyCentre for Biotechnology and Biomedicine, Institute of Immunology, College of Veterinary Medicine, University of Leipzig, Leipzig, GermanyMikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyMedical Immunology Campus Erlangen, FAU Erlangen-Nürnberg, Erlangen, GermanyMikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyMedical Immunology Campus Erlangen, FAU Erlangen-Nürnberg, Erlangen, GermanyMedizinische Klinik 1, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyMedical Immunology Campus Erlangen, FAU Erlangen-Nürnberg, Erlangen, GermanyMedizinische Klinik 1, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyMedical Immunology Campus Erlangen, FAU Erlangen-Nürnberg, Erlangen, GermanyCryptococcus neoformans is an opportunistic fungal pathogen preferentially causing disease in immunocompromised individuals such as organ-transplant-recipients, patients receiving immunosuppressive medications or, in particular, individuals suffering from HIV infection. Numerous studies clearly indicated that the control of C. neoformans infections is strongly dependent on a prototypic type 1 immune response and classical macrophage activation, whereas type 2-biased immunity and alternative activation of macrophages has been rather implicated in disease progression and detrimental outcomes. However, little is known about regulatory pathways modulating and balancing immune responses during early phases of pulmonary cryptococcosis. Here, we analyzed the role of group 2 innate lymphoid cells (ILC2s) for the control of C. neoformans infection. Using an intranasal infection model with a highly virulent C. neoformans strain, we found that ILC2 numbers were strongly increased in C. neoformans-infected lungs along with induction of a type 2 response. Mice lacking ILC2s due to conditional deficiency of the transcription factor RAR-related orphan receptor alpha (Rora) displayed a massive downregulation of features of type 2 immunity as reflected by reduced levels of the type 2 signature cytokines IL-4, IL-5, and IL-13 at 14 days post-infection. Moreover, ILC2 deficiency was accompanied with increased type 1 immunity and classical macrophage activation, while the pulmonary numbers of eosinophils and alternatively activated macrophages were reduced in these mice. Importantly, this shift in pulmonary macrophage polarization in ILC2-deficient mice correlated with improved fungal control and prolonged survival of infected mice. Conversely, adoptive transfer of ILC2s was associated with a type 2 bias associated with less efficient anti-fungal immunity in lungs of recipient mice. Collectively, our date indicate a non-redundant role of ILC2 in orchestrating myeloid anti-cryptococcal immune responses toward a disease exacerbating phenotype.https://www.frontiersin.org/article/10.3389/fimmu.2020.00209/fullILC2fungi (Candida, Cryptococcus)innate immunitylung infectiontype 2 immune response |
| spellingShingle | Markus Kindermann Lisa Knipfer Stephanie Obermeyer Uwe Müller Gottfried Alber Christian Bogdan Christian Bogdan Ulrike Schleicher Ulrike Schleicher Markus F. Neurath Markus F. Neurath Stefan Wirtz Stefan Wirtz Group 2 Innate Lymphoid Cells (ILC2) Suppress Beneficial Type 1 Immune Responses During Pulmonary Cryptococcosis Frontiers in Immunology ILC2 fungi (Candida, Cryptococcus) innate immunity lung infection type 2 immune response |
| title | Group 2 Innate Lymphoid Cells (ILC2) Suppress Beneficial Type 1 Immune Responses During Pulmonary Cryptococcosis |
| title_full | Group 2 Innate Lymphoid Cells (ILC2) Suppress Beneficial Type 1 Immune Responses During Pulmonary Cryptococcosis |
| title_fullStr | Group 2 Innate Lymphoid Cells (ILC2) Suppress Beneficial Type 1 Immune Responses During Pulmonary Cryptococcosis |
| title_full_unstemmed | Group 2 Innate Lymphoid Cells (ILC2) Suppress Beneficial Type 1 Immune Responses During Pulmonary Cryptococcosis |
| title_short | Group 2 Innate Lymphoid Cells (ILC2) Suppress Beneficial Type 1 Immune Responses During Pulmonary Cryptococcosis |
| title_sort | group 2 innate lymphoid cells ilc2 suppress beneficial type 1 immune responses during pulmonary cryptococcosis |
| topic | ILC2 fungi (Candida, Cryptococcus) innate immunity lung infection type 2 immune response |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00209/full |
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