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In vivo Neutralization of Pro-inflammatory Cytokines During Secondary Streptococcus pneumoniae Infection Post Influenza A Virus Infection
Sharma-Chawla, Niharika Stegemann-Koniszewski, Sabine Christen, Henrike Boehme, Julia D. Kershaw, Olivia Schreiber, Jens Guzmán, Carlos A. Bruder, Dunja Hernandez-Vargas, Esteban A.
Sharma-Chawla, Niharika
Stegemann-Koniszewski, Sabine
Christen, Henrike
Boehme, Julia D.
Kershaw, Olivia
Schreiber, Jens
Guzmán, Carlos A.
Bruder, Dunja
Hernandez-Vargas, Esteban A.
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2019-08-14
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Abstract
An overt pro-inflammatory immune response is a key factor contributing to lethal pneumococcal infection in an influenza pre-infected host and represents a potential target for therapeutic intervention. However, there is a paucity of knowledge about the level of contribution of individual cytokines. Based on the predictions of our previous mathematical modeling approach, the potential benefit of IFN-γ- and/or IL-6-specific antibody-mediated cytokine neutralization was explored in C57BL/6 mice infected with the influenza A/PR/8/34 strain, which were subsequently infected with the Streptococcus pneumoniae strain TIGR4 on day 7 post influenza. While single IL-6 neutralization had no effect on respiratory bacterial clearance, single IFN-γ neutralization enhanced local bacterial clearance in the lungs. Concomitant neutralization of IFN-γ and IL-6 significantly reduced the degree of pneumonia as well as bacteremia compared to the control group, indicating a positive effect for the host during secondary bacterial infection. The results of our model-driven experimental study reveal that the predicted therapeutic value of IFN-γ and IL-6 neutralization in secondary pneumococcal infection following influenza infection is tightly dependent on the experimental protocol while at the same time paving the way toward the development of effective immune therapies.
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Front Immunol. 2019 Aug 14;10:1864. doi: 10.3389/fimmu.2019.01864. eCollection 2019.
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en
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1664-3224
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Attribution-NonCommercial-ShareAlike 4.0 International