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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #384456

Research Project: Nutrition, Immune and Inflammatory Responses, and Related Diseases

Location: Jean Mayer Human Nutrition Research Center On Aging

Title: A murine model for the transition of Streptococcus pneumoniae from asymptomatic colonizer to systemic pathogen

item JOMA, BASMA - Tufts University
item SIWAPORNCHAI, NALAT - Tufts University
item VANGURI, VIJAY - University Of Massachusetts
item SHRESTHA, ANISHMA - Tufts University
item ROGGENSACK, SARA - Tufts University
item DAVIDSON, BRUCE - University Of Buffalo
item TAI, ALBERT - Tufts University
item HAKANSSON, ANDERS - Lund University
item MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item LEONG, JOHN - Tufts University
item BOU GHANEM, ELSA - Tufts University

Submitted to: American Society for Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/10/2021
Publication Date: 7/15/2021
Citation: Joma, B.H., Siwapornchai, N., Vanguri, V.K., Shrestha, A., Roggensack, S.E., Davidson, B.A., Tai, A.K., Hakansson, A.P., Meydani, S.N., Leong, J.M., Bou Ghanem, E.N. 2021. A murine model for the transition of Streptococcus pneumoniae from asymptomatic colonizer to systemic pathogen. American Society for Microbiology.

Interpretive Summary: Streptococcus pneumoniae bacteria (pneumococcus) is usually found in the nose and throat of healthy people without symptoms. Older adults have a higher risk of being infected by viruses such as the flu that can cause these pneumococcus bacteria to move from the nose and throat to lungs and cause pneumonia and other infectious diseases. In older adults, pneumococcus infection often follows flu infection, often resulting in more severe outcomes. In this experiment, we built an accurate mouse model for flu and pneumococcus co-infection to help us better understand how age and nutrition can modify bacterial-viral co-infection behavior and immune response to it and, thus, change the morbidity and mortality from it.

Technical Abstract: Streptococcus pneumoniae (pneumococcus) resides asymptomatically in the nasopharynx but, as a pathobiont, 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 establishing pneumococcal nasopharyngeal colonization in mice, 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, concomitant disease and mortality in a fraction of mice. Although neutrophils are critical for pneumococcal clearance, IAV infection was associated with inefficient killing of pneumococci by neutrophils ex vivo and these cells were dispensable for host resistance during co-infection. In old mice (20-22 months), co-infection resulted in earlier and more severe disease compared to young mice. Aging was not associated with greater bacterial spread from the nasopharynx to the lungs or bloodstream. Rather, old mice displayed a more rapid proinflammatory cytokine response, earlier pulmonary neutrophil influx, lung damage and abrogated neutrophil function. Thus, in this model, IAV fosters the transition of pneumococci from commensals to pathogens through modifying bacterial behavior in the nasopharynx, enhancing pulmonary infection, and compromising neutrophil function. This model faithfully replicates age-associated susceptibility and can provide insight into factors that influence pathobiont behavior in different hosts.