Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection.

Ocular HSV-1 infection is a major cause of eye disease and innate and adaptive immunity both play a role in protection and pathology associated with ocular infection. Previously we have shown that M1-type macrophages are the major and earliest infiltrates into the cornea of infected mice. We also sh...

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Autores principales:	Ujjaldeep Jaggi, Harry H Matundan, Jack Yu, Satoshi Hirose, Mathias Mueller, Floyd L Wormley, Homayon Ghiasi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/fc977b80a51a4b22958b32729e59586c
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spelling	oai:doaj.org-article:fc977b80a51a4b22958b32729e59586c2021-12-02T20:00:00ZEssential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection.1553-73661553-737410.1371/journal.ppat.1009999https://doaj.org/article/fc977b80a51a4b22958b32729e59586c2021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009999https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Ocular HSV-1 infection is a major cause of eye disease and innate and adaptive immunity both play a role in protection and pathology associated with ocular infection. Previously we have shown that M1-type macrophages are the major and earliest infiltrates into the cornea of infected mice. We also showed that HSV-1 infectivity in the presence and absence of M2-macrophages was similar to wild-type (WT) control mice. However, it is not clear whether the absence of M1 macrophages plays a role in protection and disease in HSV-1 infected mice. To explore the role of M1 macrophages in HSV-1 infection, we used mice lacking M1 activation (M1-/- mice). Our results showed that macrophages from M1-/- mice were more susceptible to HSV-1 infection in vitro than were macrophages from WT mice. M1-/- mice were highly susceptible to ocular infection with virulent HSV-1 strain McKrae, while WT mice were refractory to infection. In addition, M1-/- mice had higher virus titers in the eyes than did WT mice. Adoptive transfer of M1 macrophages from WT mice to M1-/- mice reduced death and rescued virus replication in the eyes of infected mice. Infection of M1-/- mice with avirulent HSV-1 strain KOS also increased ocular virus replication and eye disease but did not affect latency-reactivation seen in WT control mice. Severity of virus replication and eye disease correlated with significantly higher inflammatory responses leading to a cytokine storm in the eyes of M1-/- infected mice that was not seen in WT mice. Thus, for the first time, our study illustrates the importance of M1 macrophages specifically in primary HSV-1 infection, eye disease, and survival but not in latency-reactivation.Ujjaldeep JaggiHarry H MatundanJack YuSatoshi HiroseMathias MuellerFloyd L WormleyHomayon GhiasiPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 10, p e1009999 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Ujjaldeep Jaggi Harry H Matundan Jack Yu Satoshi Hirose Mathias Mueller Floyd L Wormley Homayon Ghiasi Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection.
description	Ocular HSV-1 infection is a major cause of eye disease and innate and adaptive immunity both play a role in protection and pathology associated with ocular infection. Previously we have shown that M1-type macrophages are the major and earliest infiltrates into the cornea of infected mice. We also showed that HSV-1 infectivity in the presence and absence of M2-macrophages was similar to wild-type (WT) control mice. However, it is not clear whether the absence of M1 macrophages plays a role in protection and disease in HSV-1 infected mice. To explore the role of M1 macrophages in HSV-1 infection, we used mice lacking M1 activation (M1-/- mice). Our results showed that macrophages from M1-/- mice were more susceptible to HSV-1 infection in vitro than were macrophages from WT mice. M1-/- mice were highly susceptible to ocular infection with virulent HSV-1 strain McKrae, while WT mice were refractory to infection. In addition, M1-/- mice had higher virus titers in the eyes than did WT mice. Adoptive transfer of M1 macrophages from WT mice to M1-/- mice reduced death and rescued virus replication in the eyes of infected mice. Infection of M1-/- mice with avirulent HSV-1 strain KOS also increased ocular virus replication and eye disease but did not affect latency-reactivation seen in WT control mice. Severity of virus replication and eye disease correlated with significantly higher inflammatory responses leading to a cytokine storm in the eyes of M1-/- infected mice that was not seen in WT mice. Thus, for the first time, our study illustrates the importance of M1 macrophages specifically in primary HSV-1 infection, eye disease, and survival but not in latency-reactivation.
format	article
author	Ujjaldeep Jaggi Harry H Matundan Jack Yu Satoshi Hirose Mathias Mueller Floyd L Wormley Homayon Ghiasi
author_facet	Ujjaldeep Jaggi Harry H Matundan Jack Yu Satoshi Hirose Mathias Mueller Floyd L Wormley Homayon Ghiasi
author_sort	Ujjaldeep Jaggi
title	Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection.
title_short	Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection.
title_full	Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection.
title_fullStr	Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection.
title_full_unstemmed	Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection.
title_sort	essential role of m1 macrophages in blocking cytokine storm and pathology associated with murine hsv-1 infection.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/fc977b80a51a4b22958b32729e59586c
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Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection.

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