The role of NK cells during bacterial and viral/bacterial co-infection

Abstract

Abstract Influenza virus is a large burden to the human population and a leading cause of death worldwide. Much of this high morbidity and mortality is due to co-infections with pulmonary bacterial pathogens, such as Streptococcus pneumoniae. Prior studies indicate that a primary influenza infection exacerbates secondary infection of S. pneumoniae in murine models. In part, this is due to increased bacterial burdens in the lung driven by pro- or anti-inflammatory cytokines such as IFNγ and IL-10. However, the cellular source(s) of these cytokines and their roles during infection is unclear. Previous work in our lab has shown that during systemic Listeria monocytogenes infection, NK cells are a critical source of early IFNγ with delayed IL-10 production and that IL-10 specifically facilitates pathogenesis. Here, we report that NK cells also increase susceptibility to pulmonary S. pneumoniae infection, as demonstrated by reduced bacterial burdens in organs following NK cell depletion. Using an in vitro BMDC/NK cell co-culture system, we further show that S. pneumoniae infection can directly elicit NK cell IL-10 production. Therefore, we hypothesize that NK cells play an important role during S. pneumoniae infection. To test whether NK cells also influence influenza/S. pneumoniae co-infection, we established a mouse model where S. pneumoniae bacterial burdens are increased in organs of co-infected mice. We are currently investigating how NK cells affect susceptibility to secondary S. pneumoniae infection and specifically the role of NK cell IL-10. Ultimately, this work has the potential to further define the mechanism(s) by which NK cells contribute to the control or pathogenesis of S. pneumoniae and influenza virus/S. pneumoniae co-infection.