Exposure to Cigarette Smoke Enhances Pneumococcal Transmission Among Littermates in an Infant Mouse Model.

Daichi Murakami,Jeffrey N Weiser,Muneki Hotomi,Masamitsu Kono,Tonia Zangari,Yasuteru Muragaki,Denisa Nanushaj,Fumie Kaneko

doi:10.3389/fcimb.2021.651495

Abstract

Streptococcus pneumoniae, one of the most common commensal pathogens among children, is spread by close contact in daycare centers or within a family. Host innate immune responses and bacterial virulence factors promote pneumococcal transmission. However, investigations into the effects of environmental factors on transmission have been limited. Passive smoking, a great concern for children’s health, has been reported to exacerbate pneumococcal diseases. Here, we describe the effect of cigarette smoke exposure on an infant mouse model of pneumococcal transmission. Our findings reveal that the effect of cigarette smoke exposure significantly promotes pneumococcal transmission by enhancing bacterial shedding from the colonized host and by increasing susceptibility to pneumococcal colonization in the new host, both of which are critical steps of transmission. Local inflammation, followed by mucosal changes (such as mucus hypersecretion and disruption of the mucosal barrier), are important underlying mechanisms for promotion of transmission by smoke exposure. These effects were attributable to the constituents of cigarette smoke rather than smoke itself. These findings provide the first experimental evidence of the impact of environmental factors on pneumococcal transmission and the mechanism of pathogenesis.

Highlights

Streptococcus pneumoniae (Sp.; the pneumococcus) is one of the leading pathogens responsible for upper respiratory infections or invasive infections during childhood
We demonstrate that cigarette smoke exposure promotes host-to-host transmission of S. pneumoniae in a neonatal mouse model by enhancing pneumococcal shedding from the colonized host and by increasing susceptibility to infection in a new host
Co-infection with influenza virus significantly increased bacterial load and neutrophil migration to the nasopharynx, which resulted in a significant increase in bacterial shedding compared to mice that were infected with Sp. alone

Summary

Introduction

Streptococcus pneumoniae (Sp.; the pneumococcus) is one of the leading pathogens responsible for upper respiratory infections or invasive infections during childhood. Host innate immunity factors such as TLR2 and TLR3 were shown to be involved in the mechanism of increased pneumococcal transmission in an IAV co-infection model (Richard et al, 2014; Kono et al, 2016). In the infant mouse model, pneumococcal mono-infection caused a subtle but acute inflammatory response which resulted in pneumococcal shedding and transmission among littermates (Zafar et al, 2016). Pneumolysin, a pivotal pneumococcal virulence factor, contributes to pneumococcal colonization density in infant mice and promotes shedding and transmission due to local inflammation caused by tissue damage (Hotomi et al, 2016; Zafar et al, 2017)

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