Limits...
Increased susceptibility for superinfection with Streptococcus pneumoniae during influenza virus infection is not caused by TLR7-mediated lymphopenia.

Stegemann S, Dahlberg S, Kröger A, Gereke M, Bruder D, Henriques-Normark B, Gunzer M - PLoS ONE (2009)

Bottom Line: We previously demonstrated that triggering of TLR7 causes immune incompetence in mice by induction of 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.

View Article: PubMed Central - PubMed

Affiliation: Otto-von-Guericke University, Institute of Molecular and Clinical Immunology, Magdeburg, Germany.

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.

Show MeSH

Related in: MedlinePlus

Forced lymphopenia does not interfere with bacterial clearance in S. pneumoniae infected hosts.C57Bl/6 mice were intranasally infected with 1×105 CFU Streptococcus pneumoniae TIGR4 and at the same time intraperitoneally injected with PBS (•) or R-848 (○). Mice were sacrificed 4 and 24 hours later and S. pneumoniae CFU counts in nasopharyngeal lavage (A), bronchoalveolar lavage (B) and lung homogenates (C) were assessed. Data show values of individual mice together with group means (horizontal lines) and are compiled from two independent experiments.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2654096&req=5

pone-0004840-g005: Forced lymphopenia does not interfere with bacterial clearance in S. pneumoniae infected hosts.C57Bl/6 mice were intranasally infected with 1×105 CFU Streptococcus pneumoniae TIGR4 and at the same time intraperitoneally injected with PBS (•) or R-848 (○). Mice were sacrificed 4 and 24 hours later and S. pneumoniae CFU counts in nasopharyngeal lavage (A), bronchoalveolar lavage (B) and lung homogenates (C) were assessed. Data show values of individual mice together with group means (horizontal lines) and are compiled from two independent experiments.

Mentions: Although TLR7-mediated lymphopenia did not affect the overall survival of S. pneumoniae-infected mice it was still possible that lymphopenia showed more subtle effects on bacterial spread. Thus we analyzed the course of bacterial deletion at three sites. As already indicated by the viability experiments, also the clearance of bacteria was unchanged in normal versus lymphopenic mice (Fig. 5).


Increased susceptibility for superinfection with Streptococcus pneumoniae during influenza virus infection is not caused by TLR7-mediated lymphopenia.

Stegemann S, Dahlberg S, Kröger A, Gereke M, Bruder D, Henriques-Normark B, Gunzer M - PLoS ONE (2009)

Forced lymphopenia does not interfere with bacterial clearance in S. pneumoniae infected hosts.C57Bl/6 mice were intranasally infected with 1×105 CFU Streptococcus pneumoniae TIGR4 and at the same time intraperitoneally injected with PBS (•) or R-848 (○). Mice were sacrificed 4 and 24 hours later and S. pneumoniae CFU counts in nasopharyngeal lavage (A), bronchoalveolar lavage (B) and lung homogenates (C) were assessed. Data show values of individual mice together with group means (horizontal lines) and are compiled from two independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654096&req=5

pone-0004840-g005: Forced lymphopenia does not interfere with bacterial clearance in S. pneumoniae infected hosts.C57Bl/6 mice were intranasally infected with 1×105 CFU Streptococcus pneumoniae TIGR4 and at the same time intraperitoneally injected with PBS (•) or R-848 (○). Mice were sacrificed 4 and 24 hours later and S. pneumoniae CFU counts in nasopharyngeal lavage (A), bronchoalveolar lavage (B) and lung homogenates (C) were assessed. Data show values of individual mice together with group means (horizontal lines) and are compiled from two independent experiments.
Mentions: Although TLR7-mediated lymphopenia did not affect the overall survival of S. pneumoniae-infected mice it was still possible that lymphopenia showed more subtle effects on bacterial spread. Thus we analyzed the course of bacterial deletion at three sites. As already indicated by the viability experiments, also the clearance of bacteria was unchanged in normal versus lymphopenic mice (Fig. 5).

Bottom Line: We previously demonstrated that triggering of TLR7 causes immune incompetence in mice by induction of 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.

View Article: PubMed Central - PubMed

Affiliation: Otto-von-Guericke University, Institute of Molecular and Clinical Immunology, Magdeburg, Germany.

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.

Show MeSH
Related in: MedlinePlus