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CD47 Plays a Role as a Negative Regulator in Inducing Protective Immune Responses to Vaccination against Influenza Virus.
J Virol. 2016 08 01; 90(15):6746-6758.JV

Abstract

An integrin-associated protein CD47, which is a ligand for the inhibitory receptor signal regulatory protein α, is expressed on B and T cells, as well as on most innate immune cells. However, the roles of CD47 in the immune responses to viral infection or vaccination remain unknown. We investigated the role of CD47 in inducing humoral immune responses after intranasal infection with virus or immunization with influenza virus-like particles (VLPs). Virus infection or vaccination with VLPs containing hemagglutinin from A/PR8/34 influenza virus induced higher levels of antigen-specific IgG2c isotype dominant antibodies in CD47-deficient (CD47KO) mice than in wild-type (WT) mice. CD47KO mice with vaccination showed greater protective efficacy against lethal challenge, as evidenced by no loss in body weight and reduced lung viral titers compared to WT mice. In addition, inflammatory responses which include cytokine production, leukocyte infiltrates, and gamma interferon-producing CD4(+) T cells, as well as an anti-inflammatory cytokine (interleukin-10), were reduced in the lungs of vaccinated CD47KO mice after challenge with influenza virus. Analysis of lymphocytes indicated that GL7(+) germinal center B cells were induced at higher levels in the draining lymph nodes of CD47KO mice compared to those in WT mice. Notably, CD47KO mice exhibited significant increases in the numbers of antigen-specific memory B cells in spleens and plasma cells in bone marrow despite their lower levels of background IgG antibodies. These results suggest that CD47 plays a role as a negative regulator in inducing protective immune responses to influenza vaccination.

IMPORTANCE

Molecular mechanisms that control B cell activation to produce protective antibodies upon viral vaccination remain poorly understood. The CD47 molecule is known to be a ligand for the inhibitory receptor signal regulatory protein α and expressed on the surfaces of most immune cell types. CD47 was previously demonstrated to play an important role in modulating the migration of monocytes, neutrophils, polymorphonuclear neutrophils, and dendritic cells into the inflamed tissues. The results of this study demonstrate new roles of CD47 in negatively regulating the induction of protective IgG antibodies, germinal center B cells, and plasma cells secreting antigen-specific antibodies, as well as macrophages, upon influenza vaccination and challenge. As a consequence, vaccinated CD47-deficient mice demonstrated better control of influenza viral infection and enhanced protection. This study provides insights into understanding the regulatory functions of CD47 in inducing adaptive immunity to vaccination.

Authors+Show Affiliations

Center for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.Center for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA. Department of Biology, Georgia State University, Atlanta, Georgia, USA.Department of Biology, Georgia State University, Atlanta, Georgia, USA.Center for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.Department of Biology, Georgia State University, Atlanta, Georgia, USA.Department of Biology, Georgia State University, Atlanta, Georgia, USA.Center for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA skang24@gsu.edu. Department of Biology, Georgia State University, Atlanta, Georgia, USA.

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

27194758

Citation

Lee, Young-Tae, et al. "CD47 Plays a Role as a Negative Regulator in Inducing Protective Immune Responses to Vaccination Against Influenza Virus." Journal of Virology, vol. 90, no. 15, 2016, pp. 6746-6758.
Lee YT, Ko EJ, Lee Y, et al. CD47 Plays a Role as a Negative Regulator in Inducing Protective Immune Responses to Vaccination against Influenza Virus. J Virol. 2016;90(15):6746-6758.
Lee, Y. T., Ko, E. J., Lee, Y., Lee, Y. N., Bian, Z., Liu, Y., & Kang, S. M. (2016). CD47 Plays a Role as a Negative Regulator in Inducing Protective Immune Responses to Vaccination against Influenza Virus. Journal of Virology, 90(15), 6746-6758. https://doi.org/10.1128/JVI.00605-16
Lee YT, et al. CD47 Plays a Role as a Negative Regulator in Inducing Protective Immune Responses to Vaccination Against Influenza Virus. J Virol. 2016 08 1;90(15):6746-6758. PubMed PMID: 27194758.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CD47 Plays a Role as a Negative Regulator in Inducing Protective Immune Responses to Vaccination against Influenza Virus. AU - Lee,Young-Tae, AU - Ko,Eun-Ju, AU - Lee,Youri, AU - Lee,Yu-Na, AU - Bian,Zhen, AU - Liu,Yuan, AU - Kang,Sang-Moo, Y1 - 2016/07/11/ PY - 2016/03/31/received PY - 2016/04/09/accepted PY - 2016/5/20/entrez PY - 2016/5/20/pubmed PY - 2017/6/3/medline SP - 6746 EP - 6758 JF - Journal of virology JO - J Virol VL - 90 IS - 15 N2 - UNLABELLED: An integrin-associated protein CD47, which is a ligand for the inhibitory receptor signal regulatory protein α, is expressed on B and T cells, as well as on most innate immune cells. However, the roles of CD47 in the immune responses to viral infection or vaccination remain unknown. We investigated the role of CD47 in inducing humoral immune responses after intranasal infection with virus or immunization with influenza virus-like particles (VLPs). Virus infection or vaccination with VLPs containing hemagglutinin from A/PR8/34 influenza virus induced higher levels of antigen-specific IgG2c isotype dominant antibodies in CD47-deficient (CD47KO) mice than in wild-type (WT) mice. CD47KO mice with vaccination showed greater protective efficacy against lethal challenge, as evidenced by no loss in body weight and reduced lung viral titers compared to WT mice. In addition, inflammatory responses which include cytokine production, leukocyte infiltrates, and gamma interferon-producing CD4(+) T cells, as well as an anti-inflammatory cytokine (interleukin-10), were reduced in the lungs of vaccinated CD47KO mice after challenge with influenza virus. Analysis of lymphocytes indicated that GL7(+) germinal center B cells were induced at higher levels in the draining lymph nodes of CD47KO mice compared to those in WT mice. Notably, CD47KO mice exhibited significant increases in the numbers of antigen-specific memory B cells in spleens and plasma cells in bone marrow despite their lower levels of background IgG antibodies. These results suggest that CD47 plays a role as a negative regulator in inducing protective immune responses to influenza vaccination. IMPORTANCE: Molecular mechanisms that control B cell activation to produce protective antibodies upon viral vaccination remain poorly understood. The CD47 molecule is known to be a ligand for the inhibitory receptor signal regulatory protein α and expressed on the surfaces of most immune cell types. CD47 was previously demonstrated to play an important role in modulating the migration of monocytes, neutrophils, polymorphonuclear neutrophils, and dendritic cells into the inflamed tissues. The results of this study demonstrate new roles of CD47 in negatively regulating the induction of protective IgG antibodies, germinal center B cells, and plasma cells secreting antigen-specific antibodies, as well as macrophages, upon influenza vaccination and challenge. As a consequence, vaccinated CD47-deficient mice demonstrated better control of influenza viral infection and enhanced protection. This study provides insights into understanding the regulatory functions of CD47 in inducing adaptive immunity to vaccination. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/27194758/CD47_Plays_a_Role_as_a_Negative_Regulator_in_Inducing_Protective_Immune_Responses_to_Vaccination_against_Influenza_Virus_ DB - PRIME DP - Unbound Medicine ER -