A Murine Model for Enhancement of Streptococcus pneumoniae Pathogenicity upon Viral Infection and Advanced Age.

Autor: Joma BH; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA.; Graduate Program in Immunology, Tufts Graduate School of Biomedical Sciences, Boston, Massachusetts, USA., Siwapornchai N; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA., Vanguri VK; UMass Memorial Health Care, University of Massachusetts Medical School, Worcester, Massachusetts, USA., Shrestha A; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA., Roggensack SE; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA.; Graduate Program in Molecular Microbiology, Tufts Graduate School of Biomedical Sciences, Boston, Massachusetts, USA., Davidson BA; Department of Anesthesiology, University at Buffalo School of Medicine, Buffalo, New York, USA., Tai AK; Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts, USA., Hakansson AP; Department of Translational Medicine, Lund University, Malmö, Sweden., Meydani SN; Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA., Leong JM; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA.; Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance at Tufts (Levy CIMAR), Boston, Massachusetts, USA., Bou Ghanem EN; Department of Microbiology and Immunology, University at Buffalo School of Medicine, Buffalo, New York, USA.
Jazyk: angličtina
Zdroj: Infection and immunity [Infect Immun] 2021 Jul 15; Vol. 89 (8), pp. e0047120. Date of Electronic Publication: 2021 Jul 15.
DOI: 10.1128/IAI.00471-20
Abstrakt: Streptococcus pneumoniae (pneumococcus) resides asymptomatically in the nasopharynx (NP) 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 coinfection. We built upon this model by first establishing pneumococcal nasopharyngeal colonization, then inoculating both the nasopharynx and lungs with IAV. In young (2-month-old) mice, coinfection triggered bacterial dispersal from the nasopharynx into the lungs, pulmonary inflammation, disease, and mortality in a fraction of mice. In aged mice (18 to 24 months), coinfection 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 alpha interferon (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 coinfection, 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.
Databáze: MEDLINE