CD200 receptor restriction of myeloid cell responses antagonizes antiviral immunity and facilitates cytomegalovirus persistence within mucosal tissue
| Autor: | Stack, G, Jones, E, Marsden, M, Stacey, MA, Snelgrove, RJ, Lacaze, P, Jacques, LC, Cuff, SM, Stanton, RJ, Gallimore, AM, Hussell, T, Wilkinson, GWG, Ghazal, P, Taylor, PR, Humphreys, IR |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
DOWN-REGULATION
HOST Lymphocyte viruses PROTEIN Cytomegalovirus Fluorescent Antibody Technique MACROPHAGE ACTIVATION Mice 0302 clinical medicine 1108 Medical Microbiology INFLUENZA INFECTION Biology (General) Receptor Oligonucleotide Array Sequence Analysis Mice Knockout 0303 health sciences Membrane Glycoproteins Effector Flow Cytometry 3. Good health medicine.anatomical_structure 1107 Immunology Cytomegalovirus Infections MOUSE-CYTOMEGALOVIRUS medicine.symptom Life Sciences & Biomedicine 0605 Microbiology Research Article QH301-705.5 SALIVARY-GLANDS Immunology Congenital cytomegalovirus infection Inflammation VIRUS-INFECTION Biology Microbiology 03 medical and health sciences INFLAMMATION Downregulation and upregulation Antigens CD Virology Genetics medicine Animals Molecular Biology 030304 developmental biology MURINE CYTOMEGALOVIRUS Science & Technology Innate immune system Mucous Membrane Macrophages RC581-607 medicine.disease R1 Mice Inbred C57BL Disease Models Animal Viral replication Parasitology Immunologic diseases. Allergy 030215 immunology |
| Zdroj: | Stack, G, Jones, E, Marsden, M, Stacey, M A, Snelgrove, R J, Lacaze, P, Jacques, L C, Cuff, S M, Stanton, R J, Gallimore, A M, Hussell, T, Wilkinson, G W G, Ghazal, P, Taylor, P R & Humphreys, I R 2015, ' CD200 receptor restriction of myeloid cell responses antagonizes antiviral immunity and facilitates cytomegalovirus persistence within mucosal tissue ', PLoS Pathogens, vol. 11, no. 2, e1004641 . https://doi.org/10.1371/journal.ppat.1004641 PLoS Pathogens, Vol 11, Iss 2, p e1004641 (2015) PLoS Pathogens PLOS Pathogens |
| ISSN: | 1553-7366 |
| DOI: | 10.1371/journal.ppat.1004641 |
| Popis: | CD200 receptor (CD200R) negatively regulates peripheral and mucosal innate immune responses. Viruses, including herpesviruses, have acquired functional CD200 orthologs, implying that viral exploitation of this pathway is evolutionary advantageous. However, the role that CD200R signaling plays during herpesvirus infection in vivo requires clarification. Utilizing the murine cytomegalovirus (MCMV) model, we demonstrate that CD200R facilitates virus persistence within mucosal tissue. Specifically, MCMV infection of CD200R-deficient mice (CD200R-/-) elicited heightened mucosal virus-specific CD4 T cell responses that restricted virus persistence in the salivary glands. CD200R did not directly inhibit lymphocyte effector function. Instead, CD200R-/- mice exhibited enhanced APC accumulation that in the mucosa was a consequence of elevated cellular proliferation. Although MCMV does not encode an obvious CD200 homolog, productive replication in macrophages induced expression of cellular CD200. CD200 from hematopoietic and non-hematopoietic cells contributed independently to suppression of antiviral control in vivo. These results highlight the CD200-CD200R pathway as an important regulator of antiviral immunity during cytomegalovirus infection that is exploited by MCMV to establish chronicity within mucosal tissue. Author Summary Immune inhibitory receptors, including CD200 receptor (CD200R), can limit immune responses in the mucosa to restrict reactivity to the plethora of harmless antigens that mucosal surfaces are continually exposed to. However, viruses may exploit these suppressive mechanisms to enable their persistence and spread. Many viruses, including herpesviruses, have acquired functional homologs of CD200, the ligand of CD200R, implying that viral exploitation of this pathway is evolutionary advantageous. We now show that the β-herpesvirus murine cytomegalovirus (MCMV) takes advantage of the CD200R inhibitory pathway to persist within a mucosal site of MCMV persistence, the salivary glands. Mice deficient in CD200R mounted elevated antiviral immune responses that were driven by the increased division and accumulation of myeloid cells that function to orchestrate the generation of antiviral effector immune responses. Interestingly, MCMV infection of myeloid cells up-regulated CD200 expression. Thus, MCMV exploits the CD200 pathway to persist within mucosal tissue. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|