tetano
Editor, Senior Moderator
PLoS Pathog
. 2021 Mar 9;17(3):e1009405.
doi: 10.1371/journal.ppat.1009405. Online ahead of print.
Sequential targeting of interferon pathways for increased host resistance to bacterial superinfection during influenza
Tarani Kanta Barman[SUP] 1 [/SUP], Rachael Racine[SUP] 1 [/SUP], Jesse L Bonin[SUP] 1 [/SUP], Danielle Califano[SUP] 1 [/SUP], Sharon L Salmon[SUP] 1 [/SUP], Dennis W Metzger[SUP] 1 [/SUP]
Affiliations
Abstract
Bacterial co-infections represent a major clinical complication of influenza. Host-derived interferon (IFN) increases susceptibility to bacterial infections following influenza, but the relative roles of type-I versus type-II IFN remain poorly understood. We have used novel mouse models of co-infection in which colonizing pneumococci were inoculated into the upper respiratory tract; subsequent sublethal influenza virus infection caused the bacteria to enter the lungs and mediate lethal disease. Compared to wild-type mice or mice deficient in only one pathway, mice lacking both IFN pathways demonstrated the least amount of lung tissue damage and mortality following pneumococcal-influenza virus superinfection. Therapeutic neutralization of both type-I and type-II IFN pathways similarly provided optimal protection to co-infected wild-type mice. The most effective treatment regimen was staggered neutralization of the type-I IFN pathway early during co-infection combined with later neutralization of type-II IFN, which was consistent with the expression and reported activities of these IFNs during superinfection. These results are the first to directly compare the activities of type-I and type-II IFN during superinfection and provide new insights into potential host-directed targets for treatment of secondary bacterial infections during influenza.
. 2021 Mar 9;17(3):e1009405.
doi: 10.1371/journal.ppat.1009405. Online ahead of print.
Sequential targeting of interferon pathways for increased host resistance to bacterial superinfection during influenza
Tarani Kanta Barman[SUP] 1 [/SUP], Rachael Racine[SUP] 1 [/SUP], Jesse L Bonin[SUP] 1 [/SUP], Danielle Califano[SUP] 1 [/SUP], Sharon L Salmon[SUP] 1 [/SUP], Dennis W Metzger[SUP] 1 [/SUP]
Affiliations
- PMID: 33690728
- DOI: 10.1371/journal.ppat.1009405
Abstract
Bacterial co-infections represent a major clinical complication of influenza. Host-derived interferon (IFN) increases susceptibility to bacterial infections following influenza, but the relative roles of type-I versus type-II IFN remain poorly understood. We have used novel mouse models of co-infection in which colonizing pneumococci were inoculated into the upper respiratory tract; subsequent sublethal influenza virus infection caused the bacteria to enter the lungs and mediate lethal disease. Compared to wild-type mice or mice deficient in only one pathway, mice lacking both IFN pathways demonstrated the least amount of lung tissue damage and mortality following pneumococcal-influenza virus superinfection. Therapeutic neutralization of both type-I and type-II IFN pathways similarly provided optimal protection to co-infected wild-type mice. The most effective treatment regimen was staggered neutralization of the type-I IFN pathway early during co-infection combined with later neutralization of type-II IFN, which was consistent with the expression and reported activities of these IFNs during superinfection. These results are the first to directly compare the activities of type-I and type-II IFN during superinfection and provide new insights into potential host-directed targets for treatment of secondary bacterial infections during influenza.