Year-end Sale % OFF 
Abstract
Influenza A virus (IAV) causes respiratory tract infections leading to recurring epidemics with high rates of morbidity and mortality. In the past century IAV induced several world-wide pandemics, the most aggressive occurring in 1918 with a death toll of 20–50 million cases. However, infection with IAV alone is rarely fatal. Instead, death associated with IAV is usually mediated by superinfection with bacteria, mainly Streptococcus pneumoniae. The reasons for this increased susceptibility to bacterial superinfection have not been fully elucidated. We previously demonstrated that triggering of TLR7 causes immune incompetence in mice by induction of lymphopenia. IAV is recognized by TLR7 and infections can lead to lymphopenia. Since lymphocytes are critical to protect from S. pneumoniae it has long been speculated that IAV-induced lymphopenia might mediate increased susceptibility to superinfection. Here we show that sub-lethal pre-infections of mice with IAV-PR8/A/34 strongly increased their mortality in non-lethal SP infections, surprisingly despite the absence of detectable lymphopenia. In contrast to SP-infection alone co-infected animals were unable to control the exponential growth of SP. However, lymphopenia forced by TLR7-triggering or antibody-mediated neutropenia did not increase SP-susceptibility or compromise the ability to control SP growth. Thus, the immune-incompetence caused by transient lympho- or leukopenia is not sufficient to inhibit potent antibacterial responses of the host and mechanisms distinct from leukodepletion must account for increased bacterial superinfection during viral defence.
Highlights
Influenza A virus (IAV) belongs to the class of orthomyxoviridae [1,2] and presents with high genetic variability which is the cause for regularly occurring epidemics [2] or world-wide pandemics [3]
To establish a model system for IAV/S. pneumoniae synergism in the mouse we established two sublethal infections with either the mouse-adapted viral strain PR8/A/34 or the pneumococcal strain TIGR4. 0.04 MLD50 of IAV caused a mild disease with a transient mean loss of max. 10% body weight up to day 7 of the infection, which was resolved by day 12 post infection (Fig. 1A)
Survival-curves showed that both infections were sublethal to 80% (IAV) or 88% (S. pneumoniae) of all animals single individuals could still succumb to the infection as seen elsewhere [10]
Summary
Influenza A virus (IAV) belongs to the class of orthomyxoviridae [1,2] and presents with high genetic variability which is the cause for regularly occurring epidemics [2] or world-wide pandemics [3]. The major reason for this large mortality was not the IAVinfection per se but rather secondary bacterial superinfections, often caused by Streptococcus pneumoniae [7,8] Supporting this notion, vaccination against S. pneumoniae can prevent 31% of IAVassociated pneumonias [9]. S. pneumoniae is a Gram-positive, encapsulated, facultatively anaerobic bacterium [11] that is considered the most common bacterial respiratory tract pathogen. It causes otitis media and sinusitis, but is a major contributor to community acquired pneumonia with mortality rates as high as 20% in patients with concurrent septicaemia [11,12,13]. CD4+ T cells have been implicated in the early control of the infection [11,15,16]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
