Streptococcus pneumoniae coinfection dictates susceptibility to oral Listeria monocytogenes through suppressive Natural Killer (NK) cell activity

Abstract

Abstract Coinfection with viral and bacterial pathogens is a major health concern and results in significant morbidity and mortality. Recent research has aimed to understand the complex interplay between multiple pathogens and the immune response during viral:bacterial coinfections. However, studies using bacterial-bacterial coinfections are lacking. Streptococcus pneumoniae (Spn) and Listeria monocytogenes (Lm) are both bacterial pathogens that are capable of causing severe infections in young, elderly, and immunocompromised populations. Here we show that coinfection with intratracheal (IT) Spn increases susceptibility of typically resistant mice to oral Lm infection. On day 3 post infection (p.i.), the presence of Spn increased oral Lm burdens in the spleen, liver, and lungs of coinfected C57/BL6 mice. In addition, while the anti-inflammatory cytokine Interleukin-10 (IL-10) is limited during oral Lm infection, Spn infection induced the production of IL-10 from Natural Killer (NK) cells, and that this correlated with an increase in Lm burdens during coinfection. To assess the importance of NK cell IL-10 in the absence of an ongoing infection, mice were inoculated with a recombinant Lm polypeptide, designated L1S, which stimulates NK cell IL-10 production. In the presence of L1S, the induction of NK cell IL-10 similarly increased systemic burdens of oral Lm. Lastly, BMMs stimulated with rIL-10 and infected with Lm have increased bacterial burdens when compared to untreated but infected controls. Overall, our data show that coinfection impairs host protection through the induction of NK cell production of IL-10 and dictates susceptibility to oral Lm infection.