IL-27 Receptor Signaling Regulates Memory CD4 + T Cell Populations and Suppresses Rapid Inflammatory Responses during Secondary Malaria Infection
| Autor: | Emily Gwyer Findlay, Ana Villegas-Mendez, J. Brian de Souza, Eleanor M. Riley, Lisa M Grady, Noelle O'Regan, Christiaan J. M. Saris, Kevin N. Couper |
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| Rok vydání: | 2014 |
| Předmět: |
CD4-Positive T-Lymphocytes
Plasmodium berghei Secondary infection T cell Immunology Population Cell Count Mice Transgenic Inflammation Spleen Parasitemia Biology Microbiology Mice Immune system medicine Animals education Immunity Cellular Host Response and Inflammation education.field_of_study Interleukins Receptors Interleukin medicine.disease biology.organism_classification Malaria Mice Inbred C57BL Disease Models Animal Infectious Diseases medicine.anatomical_structure Liver Cytokines Parasitology medicine.symptom Signal Transduction |
| Zdroj: | Infection and Immunity. 82:10-20 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.01091-13 |
| Popis: | Interleukin-27 (IL-27) is known to control primary CD4 + T cell responses during a variety of different infections, but its role in regulating memory CD4 + T responses has not been investigated in any model. In this study, we have examined the functional importance of IL-27 receptor (IL-27R) signaling in regulating the formation and maintenance of memory CD4 + T cells following malaria infection and in controlling their subsequent reactivation during secondary parasite challenge. We demonstrate that although the primary effector/memory CD4 + T cell response was greater in IL-27R-deficient (WSX-1 −/− ) mice following Plasmodium berghei NK65 infection than in wild-type (WT) mice, there were no significant differences in the size of the maintained memory CD4 + T population(s) at 20 weeks postinfection in the spleen, liver, or bone marrow of WSX-1 −/− mice compared with WT mice. However, the composition of the memory CD4 + T cell pool was slightly altered in WSX-1 −/− mice following clearance of primary malaria infection, with elevated numbers of late effector memory CD4 + T cells in the spleen and liver and increased production of IL-2 in the spleen. Crucially, WSX-1 −/− mice displayed significantly enhanced parasite control compared with WT mice following rechallenge with homologous malaria parasites. Improved parasite control in WSX-1 −/− mice during secondary infection was associated with elevated systemic production of multiple inflammatory innate and adaptive cytokines and extremely rapid proliferation of antigen-experienced T cells in the liver. These data are the first to demonstrate that IL-27R signaling plays a role in regulating the magnitude and quality of secondary immune responses during rechallenge infections. |
| Databáze: | OpenAIRE |
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