Neuropilin-1 Regulates the Secondary CD8 T Cell Response to Virus Infection

ABSTRACT Neuropilin-1 (Nrp1) plays important roles in axonal guidance in neurons and in the growth of new blood vessels. There is also a growing appreciation for roles played by neuropilin-1 in the immune response. This molecule is important for the function of regulatory T cells; however, roles in...

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Autores principales:	Ji Young Hwang, Yanbo Sun, Christopher R. Carroll, Edward J. Usherwood
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Kaposi’s sarcoma-associated herpesvirus T cells immune memory Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6bd1a1c403354de7b08547598013d67a
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spelling	oai:doaj.org-article:6bd1a1c403354de7b08547598013d67a2021-11-15T15:22:20ZNeuropilin-1 Regulates the Secondary CD8 T Cell Response to Virus Infection10.1128/mSphere.00221-192379-5042https://doaj.org/article/6bd1a1c403354de7b08547598013d67a2019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00221-19https://doaj.org/toc/2379-5042ABSTRACT Neuropilin-1 (Nrp1) plays important roles in axonal guidance in neurons and in the growth of new blood vessels. There is also a growing appreciation for roles played by neuropilin-1 in the immune response. This molecule is important for the function of regulatory T cells; however, roles in other T cell populations have not been identified. Here, we show that neuropilin-1 is expressed during the peak of the antiviral CD8 T cell response during murine gammaherpesvirus infection. Using a conditional knockout model, we deleted Nrp1 either before infection or after CD8 T cell memory had been established. We found that deletion of Nrp1 skewed the acute CD8 T cell response toward a memory precursor-like phenotype; however, the ensuing resting memory response was similar regardless of Nrp1 expression. Interestingly, Nrp1 deletion had differing effects on the recall response depending on the timing of deletion. When deleted before infection, Nrp1 deficiency inhibited the secondary response. Deletion just prior to reexposure to virus led to an enhanced secondary response. Interestingly, these effects were observed only in mice infected with a persistent strain of murine gammaherpesvirus and not with a nonpersistent mutant strain. These data highlight a multifaceted role for neuropilin-1 in memory CD8 T cell differentiation, dependent upon the stage of the T cell response and characteristics of the infectious agent. Several therapeutic anticancer therapies focus on inhibition of Nrp1 to restrict tumor growth, and so knowledge of how Nrp1 blockade may affect the CD8 T cell response will provide a better understanding of treatment consequences. IMPORTANCE CD8 T cell responses are critical to control both virus infections and tumors. The ability of these cells to persist for long periods of time can result in lifelong immunity, as relatively small populations of cells can expand rapidly to counter reexposure to the same insult. Understanding the molecules necessary for this rapid secondary expansion is critical if we are to develop therapies that can provide lifelong protection. This report shows an important and complex role for the molecule neuropilin-1 in the secondary response. Several cancer therapies targeting neuropilin-1 are in development, and this work will lead to better understanding of the effect these therapies could have upon the protective CD8 T cell response.Ji Young HwangYanbo SunChristopher R. CarrollEdward J. UsherwoodAmerican Society for MicrobiologyarticleKaposi’s sarcoma-associated herpesvirusT cellsimmune memoryMicrobiologyQR1-502ENmSphere, Vol 4, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Kaposi’s sarcoma-associated herpesvirus T cells immune memory Microbiology QR1-502
spellingShingle	Kaposi’s sarcoma-associated herpesvirus T cells immune memory Microbiology QR1-502 Ji Young Hwang Yanbo Sun Christopher R. Carroll Edward J. Usherwood Neuropilin-1 Regulates the Secondary CD8 T Cell Response to Virus Infection
description	ABSTRACT Neuropilin-1 (Nrp1) plays important roles in axonal guidance in neurons and in the growth of new blood vessels. There is also a growing appreciation for roles played by neuropilin-1 in the immune response. This molecule is important for the function of regulatory T cells; however, roles in other T cell populations have not been identified. Here, we show that neuropilin-1 is expressed during the peak of the antiviral CD8 T cell response during murine gammaherpesvirus infection. Using a conditional knockout model, we deleted Nrp1 either before infection or after CD8 T cell memory had been established. We found that deletion of Nrp1 skewed the acute CD8 T cell response toward a memory precursor-like phenotype; however, the ensuing resting memory response was similar regardless of Nrp1 expression. Interestingly, Nrp1 deletion had differing effects on the recall response depending on the timing of deletion. When deleted before infection, Nrp1 deficiency inhibited the secondary response. Deletion just prior to reexposure to virus led to an enhanced secondary response. Interestingly, these effects were observed only in mice infected with a persistent strain of murine gammaherpesvirus and not with a nonpersistent mutant strain. These data highlight a multifaceted role for neuropilin-1 in memory CD8 T cell differentiation, dependent upon the stage of the T cell response and characteristics of the infectious agent. Several therapeutic anticancer therapies focus on inhibition of Nrp1 to restrict tumor growth, and so knowledge of how Nrp1 blockade may affect the CD8 T cell response will provide a better understanding of treatment consequences. IMPORTANCE CD8 T cell responses are critical to control both virus infections and tumors. The ability of these cells to persist for long periods of time can result in lifelong immunity, as relatively small populations of cells can expand rapidly to counter reexposure to the same insult. Understanding the molecules necessary for this rapid secondary expansion is critical if we are to develop therapies that can provide lifelong protection. This report shows an important and complex role for the molecule neuropilin-1 in the secondary response. Several cancer therapies targeting neuropilin-1 are in development, and this work will lead to better understanding of the effect these therapies could have upon the protective CD8 T cell response.
format	article
author	Ji Young Hwang Yanbo Sun Christopher R. Carroll Edward J. Usherwood
author_facet	Ji Young Hwang Yanbo Sun Christopher R. Carroll Edward J. Usherwood
author_sort	Ji Young Hwang
title	Neuropilin-1 Regulates the Secondary CD8 T Cell Response to Virus Infection
title_short	Neuropilin-1 Regulates the Secondary CD8 T Cell Response to Virus Infection
title_full	Neuropilin-1 Regulates the Secondary CD8 T Cell Response to Virus Infection
title_fullStr	Neuropilin-1 Regulates the Secondary CD8 T Cell Response to Virus Infection
title_full_unstemmed	Neuropilin-1 Regulates the Secondary CD8 T Cell Response to Virus Infection
title_sort	neuropilin-1 regulates the secondary cd8 t cell response to virus infection
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/6bd1a1c403354de7b08547598013d67a
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Neuropilin-1 Regulates the Secondary CD8 T Cell Response to Virus Infection

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