TLR2 Signaling Decreases Transmission of Streptococcus pneumoniae by Limiting Bacterial Shedding in an Infant Mouse Influenza A Co-infection Model

PLoS Pathogens

Steven J. Siegel¹  Jeffrey N. Weiser¹  Aimee L. Richard¹  Jan Erikson² 

[1] Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America;The Wistar Institute, Philadelphia, Pennsylvania, United States of America

关键词: Mouse models;    Pneumococcus;    Influenza;    Inflammation;    Neutrophils;    Co-infections;    Bacterial pathogens;    Nasopharynx;   

DOI  :  10.1371/journal.ppat.1004339

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

While the importance of transmission of pathogens is widely accepted, there is currently little mechanistic understanding of this process. Nasal carriage of Streptococcus pneumoniae (the pneumococcus) is common in humans, especially in early childhood, and is a prerequisite for the development of disease and transmission among hosts. In this study, we adapted an infant mouse model to elucidate host determinants of transmission of S. pneumoniae from inoculated index mice to uninfected contact mice. In the context of co-infection with influenza A virus, the pneumococcus was transmitted among wildtype littermates, with approximately half of the contact mice acquiring colonization. Mice deficient for TLR2 were colonized to a similar density but transmitted S. pneumoniae more efficiently (100% transmission) than wildtype animals and showed decreased expression of interferon α and higher viral titers. The greater viral burden in tlr2−/− mice correlated with heightened inflammation, and was responsible for an increase in bacterial shedding from the mouse nose. The role of TLR2 signaling was confirmed by intranasal treatment of wildtype mice with the agonist Pam3Cys, which decreased inflammation and reduced bacterial shedding and transmission. Taken together, these results suggest that the innate immune response to influenza virus promotes bacterial shedding, allowing the bacteria to transit from host to host. These findings provide insight into the role of host factors in the increased pneumococcal carriage rates seen during flu season and contribute to our overall understanding of pathogen transmission.

【 授权许可】

CC BY