Cargando…

Virus-Specific Immune Memory at Peripheral Sites of Herpes Simplex Virus Type 2 (HSV-2) Infection in Guinea Pigs

Despite its importance in modulating HSV-2 pathogenesis, the nature of tissue-resident immune memory to HSV-2 is not completely understood. We used genital HSV-2 infection of guinea pigs to assess the type and location of HSV-specific memory cells at peripheral sites of HSV-2 infection. HSV-specific...

Descripción completa

Detalles Bibliográficos
Autores principales: Xia, Jingya, Veselenak, Ronald L., Gorder, Summer R., Bourne, Nigel, Milligan, Gregg N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259353/
https://www.ncbi.nlm.nih.gov/pubmed/25485971
http://dx.doi.org/10.1371/journal.pone.0114652
_version_ 1782347996866805760
author Xia, Jingya
Veselenak, Ronald L.
Gorder, Summer R.
Bourne, Nigel
Milligan, Gregg N.
author_facet Xia, Jingya
Veselenak, Ronald L.
Gorder, Summer R.
Bourne, Nigel
Milligan, Gregg N.
author_sort Xia, Jingya
collection PubMed
description Despite its importance in modulating HSV-2 pathogenesis, the nature of tissue-resident immune memory to HSV-2 is not completely understood. We used genital HSV-2 infection of guinea pigs to assess the type and location of HSV-specific memory cells at peripheral sites of HSV-2 infection. HSV-specific antibody-secreting cells were readily detected in the spleen, bone marrow, vagina/cervix, lumbosacral sensory ganglia, and spinal cord of previously-infected animals. Memory B cells were detected primarily in the spleen and to a lesser extent in bone marrow but not in the genital tract or neural tissues suggesting that the HSV-specific antibody-secreting cells present at peripheral sites of HSV-2 infection represented persisting populations of plasma cells. The antibody produced by these cells isolated from neural tissues of infected animals was functionally relevant and included antibodies specific for HSV-2 glycoproteins and HSV-2 neutralizing antibodies. A vigorous IFN-γ-secreting T cell response developed in the spleen as well as the sites of HSV-2 infection in the genital tract, lumbosacral ganglia and spinal cord following acute HSV-2 infection. Additionally, populations of HSV-specific tissue-resident memory T cells were maintained at these sites and were readily detected up to 150 days post HSV-2 infection. Unlike the persisting plasma cells, HSV-specific memory T cells were also detected in uterine tissue and cervicothoracic region of the spinal cord and at low levels in the cervicothoracic ganglia. Both HSV-specific CD4(+) and CD8(+) resident memory cell subsets were maintained long-term in the genital tract and sensory ganglia/spinal cord following HSV-2 infection. Together these data demonstrate the long-term maintenance of both humoral and cellular arms of the adaptive immune response at the sites of HSV-2 latency and virus shedding and highlight the utility of the guinea pig infection model to investigate tissue-resident memory in the setting of HSV-2 latency and spontaneous reactivation.
format Online
Article
Text
id pubmed-4259353
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-42593532014-12-15 Virus-Specific Immune Memory at Peripheral Sites of Herpes Simplex Virus Type 2 (HSV-2) Infection in Guinea Pigs Xia, Jingya Veselenak, Ronald L. Gorder, Summer R. Bourne, Nigel Milligan, Gregg N. PLoS One Research Article Despite its importance in modulating HSV-2 pathogenesis, the nature of tissue-resident immune memory to HSV-2 is not completely understood. We used genital HSV-2 infection of guinea pigs to assess the type and location of HSV-specific memory cells at peripheral sites of HSV-2 infection. HSV-specific antibody-secreting cells were readily detected in the spleen, bone marrow, vagina/cervix, lumbosacral sensory ganglia, and spinal cord of previously-infected animals. Memory B cells were detected primarily in the spleen and to a lesser extent in bone marrow but not in the genital tract or neural tissues suggesting that the HSV-specific antibody-secreting cells present at peripheral sites of HSV-2 infection represented persisting populations of plasma cells. The antibody produced by these cells isolated from neural tissues of infected animals was functionally relevant and included antibodies specific for HSV-2 glycoproteins and HSV-2 neutralizing antibodies. A vigorous IFN-γ-secreting T cell response developed in the spleen as well as the sites of HSV-2 infection in the genital tract, lumbosacral ganglia and spinal cord following acute HSV-2 infection. Additionally, populations of HSV-specific tissue-resident memory T cells were maintained at these sites and were readily detected up to 150 days post HSV-2 infection. Unlike the persisting plasma cells, HSV-specific memory T cells were also detected in uterine tissue and cervicothoracic region of the spinal cord and at low levels in the cervicothoracic ganglia. Both HSV-specific CD4(+) and CD8(+) resident memory cell subsets were maintained long-term in the genital tract and sensory ganglia/spinal cord following HSV-2 infection. Together these data demonstrate the long-term maintenance of both humoral and cellular arms of the adaptive immune response at the sites of HSV-2 latency and virus shedding and highlight the utility of the guinea pig infection model to investigate tissue-resident memory in the setting of HSV-2 latency and spontaneous reactivation. Public Library of Science 2014-12-08 /pmc/articles/PMC4259353/ /pubmed/25485971 http://dx.doi.org/10.1371/journal.pone.0114652 Text en © 2014 Xia et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Xia, Jingya
Veselenak, Ronald L.
Gorder, Summer R.
Bourne, Nigel
Milligan, Gregg N.
Virus-Specific Immune Memory at Peripheral Sites of Herpes Simplex Virus Type 2 (HSV-2) Infection in Guinea Pigs
title Virus-Specific Immune Memory at Peripheral Sites of Herpes Simplex Virus Type 2 (HSV-2) Infection in Guinea Pigs
title_full Virus-Specific Immune Memory at Peripheral Sites of Herpes Simplex Virus Type 2 (HSV-2) Infection in Guinea Pigs
title_fullStr Virus-Specific Immune Memory at Peripheral Sites of Herpes Simplex Virus Type 2 (HSV-2) Infection in Guinea Pigs
title_full_unstemmed Virus-Specific Immune Memory at Peripheral Sites of Herpes Simplex Virus Type 2 (HSV-2) Infection in Guinea Pigs
title_short Virus-Specific Immune Memory at Peripheral Sites of Herpes Simplex Virus Type 2 (HSV-2) Infection in Guinea Pigs
title_sort virus-specific immune memory at peripheral sites of herpes simplex virus type 2 (hsv-2) infection in guinea pigs
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259353/
https://www.ncbi.nlm.nih.gov/pubmed/25485971
http://dx.doi.org/10.1371/journal.pone.0114652
work_keys_str_mv AT xiajingya virusspecificimmunememoryatperipheralsitesofherpessimplexvirustype2hsv2infectioninguineapigs
AT veselenakronaldl virusspecificimmunememoryatperipheralsitesofherpessimplexvirustype2hsv2infectioninguineapigs
AT gordersummerr virusspecificimmunememoryatperipheralsitesofherpessimplexvirustype2hsv2infectioninguineapigs
AT bournenigel virusspecificimmunememoryatperipheralsitesofherpessimplexvirustype2hsv2infectioninguineapigs
AT milligangreggn virusspecificimmunememoryatperipheralsitesofherpessimplexvirustype2hsv2infectioninguineapigs