Group 2 Innate Lymphoid Cells (ILC2) Suppress Beneficial Type 1 Immune Responses During Pulmonary Cryptococcosis
Kindermann M, Knipfer L, Obermeyer S, Müller U, Alber G, Bogdan C, Schleicher U, Neurath M, Wirtz S (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 11
Article Number: 209
Abstract
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.
Authors with CRIS profile
Lisa Knipfer
Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology
Stephanie Obermeyer
Lehrstuhl für Mikrobiologie und Infektionsimmunologie
Christian Bogdan
Lehrstuhl für Mikrobiologie und Infektionsimmunologie
Ulrike Schleicher
Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene
Markus Neurath
Lehrstuhl für Innere Medizin I
Stefan Wirtz
Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology
Involved external institutions
Germany (DE)How to cite
APA:
Kindermann, M., Knipfer, L., Obermeyer, S., Müller, U., Alber, G., Bogdan, C.,... Wirtz, S. (2020). Group 2 Innate Lymphoid Cells (ILC2) Suppress Beneficial Type 1 Immune Responses During Pulmonary Cryptococcosis. Frontiers in Immunology, 11. https://doi.org/10.3389/fimmu.2020.00209
MLA:
Kindermann, Markus, et al. "Group 2 Innate Lymphoid Cells (ILC2) Suppress Beneficial Type 1 Immune Responses During Pulmonary Cryptococcosis." Frontiers in Immunology 11 (2020).
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