In vivo neutralization of pro-inflammatory cytokines during secondary streptococcus pneumoniae infection post influenza a virus infection

  • 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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Author:Niharika Sharma, Sabine Stegemann-KoniszewskiORCiD, Henrike Christen, Julia Boehme, Olivia Kershaw, Jens SchreiberORCiDGND, Carlos Guzmán, Dunja BruderGND, Esteban Abelardo Hernandez-VargasORCiDGND
Pubmed Id:
Parent Title (English):Frontiers in immunology
Publisher:Frontiers Media
Place of publication:Lausanne
Contributor(s):Masato Kubo
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/08/14
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/02/17
Tag:IFN-γ neutralization; IL-6 neutralization; Influenza Virus; Streptococcus pneumoniae; co-infection; mathematical modeling
Issue:Art. 1864
Page Number:15
First Page:1
Last Page:15
Copyright © 2019 Sharma-Chawla, Stegemann-Koniszewski, Christen, Boehme, Kershaw, Schreiber, Guzmán, Bruder and Hernandez-Vargas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Institutes:Wissenschaftliche Zentren und koordinierte Programme / Frankfurt Institute for Advanced Studies (FIAS)
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0