Low-dose mercury heightens early innate response to coxsackievirus infection in female mice

Kayla L. Penta, DeLisa Fairweather, Devon L. Shirley, Noel R. Rose, Ellen K. Silbergeld, Jennifer F. Nyland

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Results: As for male mice, mercury exposure significantly increased autoimmune myocarditis and immune infiltration into the heart. During the innate response 6 h post-infection, mercury increased expression of co-stimulatory molecules and innate immune receptors on peritoneal macrophages. At the same time point, the alternatively activated macrophage gene, arginase, was increased while the classically activated macrophage gene, inducible nitric oxide synthase, was unaffected. Expression of activation markers were decreased on peritoneal B cells with mercury exposure while T cells were unaffected. Mercury increased production of pro-inflammatory mediators in the spleen. Macrophage-recruiting chemokines and activating cytokines, such as CCL2, CCL4, and IL-6, were increased with mercury following CVB3 infection.

Conclusions: Thus, mercury treatment exacerbates autoimmune myocarditis in female mice and alters early innate signaling on peritoneal macrophages. Mercury also modulates the cytokine profile in the spleen toward a macrophage-activating milieu, and upregulates alternatively activated macrophage genes, providing evidence that mercury exposure promotes inflammation in the context of infection.

Objective: Mercury is a ubiquitous environmental contaminant with toxic outcomes over a range of exposures. In this study, we investigated the effects of mercury exposure on early immune responses to coxsackievirus B3 (CVB3) infection in a murine model of autoimmune heart disease.

Materials and methods: Female BALB/c mice, susceptible to CVB3-induced autoimmune myocarditis, were treated with mercuric chloride (200 μg/kg body weight every other day for 2 weeks) prior to infection with CVB3. Six hours post-infection, immune cells were isolated from the spleen and peritoneum for flow cytometry, gene expression, and cytokine profiling. Thirty-five days post-infection, hearts were collected for histological examination of immune cell infiltration.

Original languageEnglish (US)
Pages (from-to)31-40
Number of pages10
JournalInflammation Research
Volume64
Issue number1
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Coxsackievirus Infections
Mercury
Macrophages
Myocarditis
Spleen
Peritoneal Macrophages
Cytokines
Infection
Genes
Arginase
Mercuric Chloride
Enterovirus
Poisons
Peritoneum
Gene Expression Profiling
Nitric Oxide Synthase Type II
Chemokines
Autoimmune Diseases
Heart Diseases
Interleukin-6

Keywords

  • Autoimmunity
  • Coxsackievirus
  • Cytokine
  • Innate immunity
  • Mercury

ASJC Scopus subject areas

  • Pharmacology
  • Immunology
  • Medicine(all)

Cite this

Low-dose mercury heightens early innate response to coxsackievirus infection in female mice. / Penta, Kayla L.; Fairweather, DeLisa; Shirley, Devon L.; Rose, Noel R.; Silbergeld, Ellen K.; Nyland, Jennifer F.

In: Inflammation Research, Vol. 64, No. 1, 2014, p. 31-40.

Research output: Contribution to journalArticle

Penta, Kayla L. ; Fairweather, DeLisa ; Shirley, Devon L. ; Rose, Noel R. ; Silbergeld, Ellen K. ; Nyland, Jennifer F. / Low-dose mercury heightens early innate response to coxsackievirus infection in female mice. In: Inflammation Research. 2014 ; Vol. 64, No. 1. pp. 31-40.
@article{ed751a98ac294fd9ba115d4b52e1545b,
title = "Low-dose mercury heightens early innate response to coxsackievirus infection in female mice",
abstract = "Results: As for male mice, mercury exposure significantly increased autoimmune myocarditis and immune infiltration into the heart. During the innate response 6 h post-infection, mercury increased expression of co-stimulatory molecules and innate immune receptors on peritoneal macrophages. At the same time point, the alternatively activated macrophage gene, arginase, was increased while the classically activated macrophage gene, inducible nitric oxide synthase, was unaffected. Expression of activation markers were decreased on peritoneal B cells with mercury exposure while T cells were unaffected. Mercury increased production of pro-inflammatory mediators in the spleen. Macrophage-recruiting chemokines and activating cytokines, such as CCL2, CCL4, and IL-6, were increased with mercury following CVB3 infection.Conclusions: Thus, mercury treatment exacerbates autoimmune myocarditis in female mice and alters early innate signaling on peritoneal macrophages. Mercury also modulates the cytokine profile in the spleen toward a macrophage-activating milieu, and upregulates alternatively activated macrophage genes, providing evidence that mercury exposure promotes inflammation in the context of infection.Objective: Mercury is a ubiquitous environmental contaminant with toxic outcomes over a range of exposures. In this study, we investigated the effects of mercury exposure on early immune responses to coxsackievirus B3 (CVB3) infection in a murine model of autoimmune heart disease.Materials and methods: Female BALB/c mice, susceptible to CVB3-induced autoimmune myocarditis, were treated with mercuric chloride (200 μg/kg body weight every other day for 2 weeks) prior to infection with CVB3. Six hours post-infection, immune cells were isolated from the spleen and peritoneum for flow cytometry, gene expression, and cytokine profiling. Thirty-five days post-infection, hearts were collected for histological examination of immune cell infiltration.",
keywords = "Autoimmunity, Coxsackievirus, Cytokine, Innate immunity, Mercury",
author = "Penta, {Kayla L.} and DeLisa Fairweather and Shirley, {Devon L.} and Rose, {Noel R.} and Silbergeld, {Ellen K.} and Nyland, {Jennifer F.}",
year = "2014",
doi = "10.1007/s00011-014-0781-x",
language = "English (US)",
volume = "64",
pages = "31--40",
journal = "Inflammation Research",
issn = "1023-3830",
publisher = "Birkhauser Verlag Basel",
number = "1",

}

TY - JOUR

T1 - Low-dose mercury heightens early innate response to coxsackievirus infection in female mice

AU - Penta, Kayla L.

AU - Fairweather, DeLisa

AU - Shirley, Devon L.

AU - Rose, Noel R.

AU - Silbergeld, Ellen K.

AU - Nyland, Jennifer F.

PY - 2014

Y1 - 2014

N2 - Results: As for male mice, mercury exposure significantly increased autoimmune myocarditis and immune infiltration into the heart. During the innate response 6 h post-infection, mercury increased expression of co-stimulatory molecules and innate immune receptors on peritoneal macrophages. At the same time point, the alternatively activated macrophage gene, arginase, was increased while the classically activated macrophage gene, inducible nitric oxide synthase, was unaffected. Expression of activation markers were decreased on peritoneal B cells with mercury exposure while T cells were unaffected. Mercury increased production of pro-inflammatory mediators in the spleen. Macrophage-recruiting chemokines and activating cytokines, such as CCL2, CCL4, and IL-6, were increased with mercury following CVB3 infection.Conclusions: Thus, mercury treatment exacerbates autoimmune myocarditis in female mice and alters early innate signaling on peritoneal macrophages. Mercury also modulates the cytokine profile in the spleen toward a macrophage-activating milieu, and upregulates alternatively activated macrophage genes, providing evidence that mercury exposure promotes inflammation in the context of infection.Objective: Mercury is a ubiquitous environmental contaminant with toxic outcomes over a range of exposures. In this study, we investigated the effects of mercury exposure on early immune responses to coxsackievirus B3 (CVB3) infection in a murine model of autoimmune heart disease.Materials and methods: Female BALB/c mice, susceptible to CVB3-induced autoimmune myocarditis, were treated with mercuric chloride (200 μg/kg body weight every other day for 2 weeks) prior to infection with CVB3. Six hours post-infection, immune cells were isolated from the spleen and peritoneum for flow cytometry, gene expression, and cytokine profiling. Thirty-five days post-infection, hearts were collected for histological examination of immune cell infiltration.

AB - Results: As for male mice, mercury exposure significantly increased autoimmune myocarditis and immune infiltration into the heart. During the innate response 6 h post-infection, mercury increased expression of co-stimulatory molecules and innate immune receptors on peritoneal macrophages. At the same time point, the alternatively activated macrophage gene, arginase, was increased while the classically activated macrophage gene, inducible nitric oxide synthase, was unaffected. Expression of activation markers were decreased on peritoneal B cells with mercury exposure while T cells were unaffected. Mercury increased production of pro-inflammatory mediators in the spleen. Macrophage-recruiting chemokines and activating cytokines, such as CCL2, CCL4, and IL-6, were increased with mercury following CVB3 infection.Conclusions: Thus, mercury treatment exacerbates autoimmune myocarditis in female mice and alters early innate signaling on peritoneal macrophages. Mercury also modulates the cytokine profile in the spleen toward a macrophage-activating milieu, and upregulates alternatively activated macrophage genes, providing evidence that mercury exposure promotes inflammation in the context of infection.Objective: Mercury is a ubiquitous environmental contaminant with toxic outcomes over a range of exposures. In this study, we investigated the effects of mercury exposure on early immune responses to coxsackievirus B3 (CVB3) infection in a murine model of autoimmune heart disease.Materials and methods: Female BALB/c mice, susceptible to CVB3-induced autoimmune myocarditis, were treated with mercuric chloride (200 μg/kg body weight every other day for 2 weeks) prior to infection with CVB3. Six hours post-infection, immune cells were isolated from the spleen and peritoneum for flow cytometry, gene expression, and cytokine profiling. Thirty-five days post-infection, hearts were collected for histological examination of immune cell infiltration.

KW - Autoimmunity

KW - Coxsackievirus

KW - Cytokine

KW - Innate immunity

KW - Mercury

UR - http://www.scopus.com/inward/record.url?scp=84922072903&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922072903&partnerID=8YFLogxK

U2 - 10.1007/s00011-014-0781-x

DO - 10.1007/s00011-014-0781-x

M3 - Article

VL - 64

SP - 31

EP - 40

JO - Inflammation Research

JF - Inflammation Research

SN - 1023-3830

IS - 1

ER -