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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.

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Analysis of peripheral blood lymphocyte counts shows no lymphopenia in the course of Influenza A virus infection.C57Bl/6 mice were intranasally inoculated with 0.04 MLD50 of Influenza A virus (IAV PR8/A/34) or medium (control) and repetitive blood samples on all animals were taken on different days p.i. The numbers of B220- (A), CD4- (B) and CD8-positive (C) cells in peripheral blood as determined by flow cytometry are shown as % relative to pre-infection levels. Data show representative results as means±s.e.m. of one out of two experiments with five mice per group.
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pone-0004840-g003: Analysis of peripheral blood lymphocyte counts shows no lymphopenia in the course of Influenza A virus infection.C57Bl/6 mice were intranasally inoculated with 0.04 MLD50 of Influenza A virus (IAV PR8/A/34) or medium (control) and repetitive blood samples on all animals were taken on different days p.i. The numbers of B220- (A), CD4- (B) and CD8-positive (C) cells in peripheral blood as determined by flow cytometry are shown as % relative to pre-infection levels. Data show representative results as means±s.e.m. of one out of two experiments with five mice per group.

Mentions: We next asked whether a reduction of peripheral white blood cells (leukopenia) was associated with the course of the viral infection, as had been demonstrated elsewhere [20]. Thus, we measured the levels of peripheral blood B cells as well as CD4 and CD8 T cells at different time points after a sublethal IAV-infection. However, we never observed lymphocyte-numbers in IAV-infected animals that were below the levels found in mock-infected controls (Fig. 3). In fact, from day 7 up to 14 p.i. the lymphocyte-numbers in IAV-infected animals were higher as compared to controls (Fig. 3).


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)

Analysis of peripheral blood lymphocyte counts shows no lymphopenia in the course of Influenza A virus infection.C57Bl/6 mice were intranasally inoculated with 0.04 MLD50 of Influenza A virus (IAV PR8/A/34) or medium (control) and repetitive blood samples on all animals were taken on different days p.i. The numbers of B220- (A), CD4- (B) and CD8-positive (C) cells in peripheral blood as determined by flow cytometry are shown as % relative to pre-infection levels. Data show representative results as means±s.e.m. of one out of two experiments with five mice per group.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0004840-g003: Analysis of peripheral blood lymphocyte counts shows no lymphopenia in the course of Influenza A virus infection.C57Bl/6 mice were intranasally inoculated with 0.04 MLD50 of Influenza A virus (IAV PR8/A/34) or medium (control) and repetitive blood samples on all animals were taken on different days p.i. The numbers of B220- (A), CD4- (B) and CD8-positive (C) cells in peripheral blood as determined by flow cytometry are shown as % relative to pre-infection levels. Data show representative results as means±s.e.m. of one out of two experiments with five mice per group.
Mentions: We next asked whether a reduction of peripheral white blood cells (leukopenia) was associated with the course of the viral infection, as had been demonstrated elsewhere [20]. Thus, we measured the levels of peripheral blood B cells as well as CD4 and CD8 T cells at different time points after a sublethal IAV-infection. However, we never observed lymphocyte-numbers in IAV-infected animals that were below the levels found in mock-infected controls (Fig. 3). In fact, from day 7 up to 14 p.i. the lymphocyte-numbers in IAV-infected animals were higher as compared to controls (Fig. 3).

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