Sex-based differences in susceptibility to SARS-CoV infection
Identifieur interne : 000D73 ( Main/Exploration ); précédent : 000D72; suivant : 000D74Sex-based differences in susceptibility to SARS-CoV infection
Auteurs : Rudragouda Channappanavar [États-Unis] ; Craig Fett [États-Unis] ; Matthias Mack [Allemagne] ; Patrick P. Ten Eyck [États-Unis] ; David K. Meyerholz [États-Unis] ; Stanley Perlman [États-Unis]Source :
- Journal of immunology (Baltimore, Md. : 1950) [ 0022-1767 ] ; 2017.
Descripteurs français
- KwdFr :
- Animaux, Antagonistes des récepteurs des oestrogènes (pharmacologie), Caractères sexuels, Charge virale, Femelle, Monocytes (immunologie), Mâle, Ovariectomie, Poumon (anatomopathologie), Poumon (immunologie), Poumon (virologie), Récepteurs des oestrogènes (métabolisme), Souris, Susceptibilité à une maladie, Syndrome respiratoire aigu sévère (anatomopathologie), Syndrome respiratoire aigu sévère (physiopathologie), Syndrome respiratoire aigu sévère (virologie), Virus du SRAS (isolement et purification), Virus du SRAS (pathogénicité).
- MESH :
- anatomopathologie : Poumon, Syndrome respiratoire aigu sévère.
- immunologie : Monocytes, Poumon.
- isolement et purification : Virus du SRAS.
- métabolisme : Récepteurs des oestrogènes.
- pathogénicité : Virus du SRAS.
- pharmacologie : Antagonistes des récepteurs des oestrogènes.
- physiopathologie : Syndrome respiratoire aigu sévère.
- virologie : Poumon, Syndrome respiratoire aigu sévère.
- Animaux, Caractères sexuels, Charge virale, Femelle, Mâle, Ovariectomie, Souris, Susceptibilité à une maladie.
English descriptors
- KwdEn :
- Animals, Disease Susceptibility, Estrogen Receptor Antagonists (pharmacology), Female, Lung (immunology), Lung (pathology), Lung (virology), Male, Mice, Monocytes (immunology), Ovariectomy, Receptors, Estrogen (metabolism), SARS Virus (isolation & purification), SARS Virus (pathogenicity), Severe Acute Respiratory Syndrome (pathology), Severe Acute Respiratory Syndrome (physiopathology), Severe Acute Respiratory Syndrome (virology), Sex Characteristics, Viral Load.
- MESH :
- chemical , metabolism : Receptors, Estrogen.
- chemical , pharmacology : Estrogen Receptor Antagonists.
- immunology : Lung, Monocytes.
- isolation & purification : SARS Virus.
- pathogenicity : SARS Virus.
- pathology : Lung, Severe Acute Respiratory Syndrome.
- physiopathology : Severe Acute Respiratory Syndrome.
- virology : Lung, Severe Acute Respiratory Syndrome.
- Animals, Disease Susceptibility, Female, Male, Mice, Ovariectomy, Sex Characteristics, Viral Load.
Abstract
Pathogenic human coronaviruses such as the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) cause acute respiratory illness. Epidemiological data from the 2002-2003 SARS epidemic and recent MERS indicate that there may be sex-dependent differences in disease outcomes. To investigate these differences, we infected male and female mice of different age groups with SARS-CoV and analyzed their susceptibility to the infection. Our results showed that male mice were more susceptible to SARS-CoV infection compared to age matched females. The degree of sex-bias to SARS-CoV infection increased with advancing age such that middle-aged mice showed much more pronounced differences compared to young mice. Enhanced susceptibility of male mice to SARS-CoV was associated with elevated virus titers, enhanced vascular leakage and alveolar edema. These changes were accompanied by increased accumulation of inflammatory monocyte macrophages (IMMs) and neutrophils in the lungs of male mice and depletion of IMMs partially protected these mice from lethal SARS. Moreover, the sex-specific differences were independent of T and B cell responses. Furthermore, ovariectomy or treating female mice with an estrogen receptor antagonist increased mortality indicating a protective effect for estrogen receptor signaling in mice infected with SARS-CoV. Together, these data suggest that sex differences in susceptibility to SARS-CoV in mice parallel those observed in patients and also identify estrogen receptor signaling as critical for protection in females.
Url:
DOI: 10.4049/jimmunol.1601896
PubMed: 28373583
PubMed Central: 5450662
Affiliations:
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Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Disease Susceptibility</term>
<term>Estrogen Receptor Antagonists (pharmacology)</term>
<term>Female</term>
<term>Lung (immunology)</term>
<term>Lung (pathology)</term>
<term>Lung (virology)</term>
<term>Male</term>
<term>Mice</term>
<term>Monocytes (immunology)</term>
<term>Ovariectomy</term>
<term>Receptors, Estrogen (metabolism)</term>
<term>SARS Virus (isolation & purification)</term>
<term>SARS Virus (pathogenicity)</term>
<term>Severe Acute Respiratory Syndrome (pathology)</term>
<term>Severe Acute Respiratory Syndrome (physiopathology)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Sex Characteristics</term>
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<term>Antagonistes des récepteurs des oestrogènes (pharmacologie)</term>
<term>Caractères sexuels</term>
<term>Charge virale</term>
<term>Femelle</term>
<term>Monocytes (immunologie)</term>
<term>Mâle</term>
<term>Ovariectomie</term>
<term>Poumon (anatomopathologie)</term>
<term>Poumon (immunologie)</term>
<term>Poumon (virologie)</term>
<term>Récepteurs des oestrogènes (métabolisme)</term>
<term>Souris</term>
<term>Susceptibilité à une maladie</term>
<term>Syndrome respiratoire aigu sévère (anatomopathologie)</term>
<term>Syndrome respiratoire aigu sévère (physiopathologie)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Virus du SRAS (isolement et purification)</term>
<term>Virus du SRAS (pathogénicité)</term>
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<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Estrogen Receptor Antagonists</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Poumon</term>
<term>Syndrome respiratoire aigu sévère</term>
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<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Monocytes</term>
<term>Poumon</term>
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<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Lung</term>
<term>Monocytes</term>
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<keywords scheme="MESH" qualifier="isolation & purification" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Virus du SRAS</term>
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</keywords>
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<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antagonistes des récepteurs des oestrogènes</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term>
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<term>Syndrome respiratoire aigu sévère</term>
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<term>Severe Acute Respiratory Syndrome</term>
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<term>Disease Susceptibility</term>
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<term>Viral Load</term>
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<term>Caractères sexuels</term>
<term>Charge virale</term>
<term>Femelle</term>
<term>Mâle</term>
<term>Ovariectomie</term>
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<front><div type="abstract" xml:lang="en"><p id="P1">Pathogenic human coronaviruses such as the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) cause acute respiratory illness. Epidemiological data from the 2002-2003 SARS epidemic and recent MERS indicate that there may be sex-dependent differences in disease outcomes. To investigate these differences, we infected male and female mice of different age groups with SARS-CoV and analyzed their susceptibility to the infection. Our results showed that male mice were more susceptible to SARS-CoV infection compared to age matched females. The degree of sex-bias to SARS-CoV infection increased with advancing age such that middle-aged mice showed much more pronounced differences compared to young mice. Enhanced susceptibility of male mice to SARS-CoV was associated with elevated virus titers, enhanced vascular leakage and alveolar edema. These changes were accompanied by increased accumulation of inflammatory monocyte macrophages (IMMs) and neutrophils in the lungs of male mice and depletion of IMMs partially protected these mice from lethal SARS. Moreover, the sex-specific differences were independent of T and B cell responses. Furthermore, ovariectomy or treating female mice with an estrogen receptor antagonist increased mortality indicating a protective effect for estrogen receptor signaling in mice infected with SARS-CoV. Together, these data suggest that sex differences in susceptibility to SARS-CoV in mice parallel those observed in patients and also identify estrogen receptor signaling as critical for protection in females.</p>
</div>
</front>
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