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This Tuesday’s paper will be on the consequences of viral/bacterial co-infection in a mouse model, focusing on bacterial transmission and its genetic determinants. As you can imagine, pathogen transmission is a hot-topic right now, especially when viruses such as influenza are involved. So have a read, critique the paper and join us on Tuesday night at 8 pm BST on the 30th of September.
The paper was published recently in PloS pathogens, see link.
For discussion, I think we should focus on these points:
- what is the model telling us? and is it a good model for this important question?
- does this paper providing convinving evidence for the role or TLR2-driven inflammation? and what is the role of influenza virus in this?
- what are the real-world consequences of viral/bacterial co-infection?
TLR2 Signaling Decreases Transmission of Streptococcus pneumoniae by Limiting Bacterial Shedding in an Infant Mouse Influenza A Co-infection Model.
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 intlr2−/− 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.
In this study, we sought to identify factors contributing to the transmission of the bacterial pathogen Streptococcus pneumoniae (the pneumococcus), a major cause of otitis media, pneumonia, and septicemia. Often found as a co-infection with other bacterial and viral pathogens, the pneumococcus is commonly carried by young children and is spread by close human contact, most likely through large droplet respiratory secretions. The specific determinants of bacterial transmission, however, have not been identified. This report details our use of an infant mouse model of transmission, which includes influenza A co-infection, to elucidate the mechanism of host-to-host transmission. We found that the inflammatory response to influenza, which is aggravated in the context of weakened host defense, promotes transmission by inducing bacterial shedding from the mouse nose. These results show how a bacterial pathogen exploits the host immune response to spread from one host to the next.