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A Murine Model for ...
A Murine Model for Enhancement of Streptococcus pneumoniae Pathogenicity Upon Viral Infection and Advanced Age
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- Joma, Basma H (author)
- Tufts University School of Medicine
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- Siwapornchai, Nalat (author)
- Tufts University School of Medicine
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- Vanguri, Vijay K (author)
- University of Massachusetts Medical School
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- Shrestha, Anishma (author)
- Tufts University School of Medicine
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- Roggensack, Sara E (author)
- Tufts University School of Medicine
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- Davidson, Bruce A (author)
- Jacobs School of Medicine and Biomedical Sciences
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- Tai, Albert K (author)
- Tufts University School of Medicine
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- Hakansson, Anders P (author)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Experimentell infektionsmedicin, Malmö,Forskargrupper vid Lunds universitet,Department of Translational Medicine,Faculty of Medicine,Experimental Infection Medicine, Malmö,Lund University Research Groups
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- Meydani, Simin N (author)
- Jean Mayer USDA Human Nutrition Research Center on Aging
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- Leong, John M (author)
- Tufts University School of Medicine
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- Bou Ghanem, Elsa N (author)
- Jacobs School of Medicine and Biomedical Sciences
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(creator_code:org_t)
- 2021
- 2021
- English.
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In: Infection and Immunity. - 1098-5522. ; 89:8
- Related links:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
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- Streptococcus pneumoniae (pneumococcus) resides asymptomatically in the nasopharynx but can progress from benign colonizer to lethal pulmonary or systemic pathogen. Both viral infection and aging are risk factors for serious pneumococcal infections. Previous work established a murine model that featured the movement of pneumococcus from the nasopharynx to the lung upon nasopharyngeal inoculation with influenza A virus (IAV) but did not fully recapitulate the severe disease associated with human co-infection. We built upon this model by first establishing pneumococcal nasopharyngeal colonization, then inoculating both the nasopharynx and lungs with IAV. In young (2 months) mice, co-infection triggered bacterial dispersal from the nasopharynx into the lungs, pulmonary inflammation, disease and mortality in a fraction of mice. In old mice (20-22 months), co-infection resulted in earlier and more severe disease. Aging was not associated with greater bacterial burdens but rather with more rapid pulmonary inflammation and damage. Both aging and IAV infection led to inefficient bacterial killing by neutrophils ex vivo Conversely, aging and pneumococcal colonization also blunted IFN-α production and increased pulmonary IAV burden. Thus, in this multistep model, IAV promotes pneumococcal pathogenicity by modifying bacterial behavior in the nasopharynx, diminishing neutrophil function, and enhancing bacterial growth in the lung, while pneumococci increase IAV burden likely by compromising a key antiviral response. Thus, this model provides a means to elucidate factors, such as age and co-infection, that promote the evolution of S. pneumoniae from asymptomatic colonizer to invasive pathogen, as well as to investigate consequences of this transition on antiviral defense.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
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Joma, Basma H
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Siwapornchai, Na ...
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Vanguri, Vijay K
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Shrestha, Anishm ...
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Roggensack, Sara ...
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Davidson, Bruce ...
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Tai, Albert K
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Hakansson, Ander ...
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Meydani, Simin N
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Leong, John M
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Bou Ghanem, Elsa ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Microbiology in ...
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Infection and Im ...
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Lund University