title: Increased susceptibility for superinfection with Streptococcus pneumoniae during influenza virus infection is not caused by TLR7-mediated lymphopenia.
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.
authors.affiliation: Otto-von-Guericke University, Institute of Molecular and Clinical Immunology, Magdeburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Stegemann
authors.forename: Sofia
authors.initials: S
authors.lastname: Dahlberg
authors.forename: Andrea
authors.initials: A
authors.lastname: Kröger
authors.forename: Marcus
authors.initials: M
authors.lastname: Gereke
authors.forename: Dunja
authors.initials: D
authors.lastname: Bruder
authors.forename: Birgitta
authors.initials: B
authors.lastname: Henriques-Normark
authors.forename: Matthias
authors.initials: M
authors.lastname: Gunzer
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004198:Disease Susceptibility; D005260:Female; D009980:Influenza A virus / Q000302:isolation & purification; D008231:Lymphopenia / Q000150:complications*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D011018:Pneumonia, Pneumococcal / Q000150:complications* / Q000276:immunology / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000302:isolation & purification; D015163:Superinfection; D051199:Toll-Like Receptor 7 / Q000502:physiology*
chemical_list: D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7