Location: Jean Mayer Human Nutrition Research Center On AgingTitle: A murine model for enhancement of Streptococcus pneumoniae pathogenicity upon viral infection and advanced age
|JOMA, BASM - Tufts University|
|SIWAPORNCHAI, NALAT - Tufts University|
|VANGURI, VIJAY - University Of Massachusetts|
|SHRESTHA, ANISHMA - Tufts University|
|ROGGENSACK, SARA - Tufts University|
|DAVIDSON, BRUCE - University Of Buffalo|
|TAI, ALBERT - Tufts University|
|HAKANSSON, ANDERS - Lund University|
|MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|LEONG, JOHN - Tufts University|
|BOU GHANEM, ELSA - University Of Buffalo|
Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/10/2021
Publication Date: 5/24/2021
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 enhancement of Streptococcus pneumoniae pathogenicity upon viral infection and advanced age. Infection and Immunity. 89(8):e00471-20. https://doi.org/10.1128/IAI.00471-20.
Interpretive Summary: Streptococcus pneumoniae (SP) is a bacteria that can cause pneumonia and as such is a major public health problem. SP can reside in the nose without causing any disease in the host. However, under certain conditions, it can progress from a non-harmful resident in the nose to a bacteria that can get to the lung, adversely impacting the lungs and other parts of the body, and result in mortality. Aging, nutrition, and previous infection with a virus (e.g. influenza infection) are risk factors that can help with conversion of the non-harmful bacterial to a harmful one. To understand the disease caused by SP and develop strategies to prevent it in human, an appropriate animal model is needed. Our goal was to develop an animal model that mimicked the disease caused by SP in human in order to study the impact of aging and nutrition on the disease progression. Using this model we found that older mice were more susceptible to infection than younger mice. We found that this age difference was because in old mice, a type of immune cells called neutrophils were not able to get rid of SP as effectively as young mice Our data show that this animal model can be used to further study the impact of age and other risk factors such as nutrition on susceptibility to and morbidity and mortality from SP, which is an important public health problem.
Technical Abstract: 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-alpha) 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.