TY  - JOUR
A1  - Sharma, Niharika
A1  - Stegemann-Koniszewski, Sabine
A1  - Christen, Henrike
A1  - Boehme, Julia
A1  - Kershaw, Olivia
A1  - Schreiber, Jens
A1  - Guzmán, Carlos
A1  - Bruder, Dunja
A1  - Hernandez-Vargas, Esteban Abelardo
T1  - In vivo neutralization of pro-inflammatory cytokines during secondary streptococcus pneumoniae infection post influenza a virus infection
T2  - Frontiers in immunology
N2  - 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.
KW  - co-infection
KW  - mathematical modeling
KW  - IFN-γ neutralization
KW  - IL-6 neutralization
KW  - Influenza Virus
KW  - Streptococcus pneumoniae
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51866
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-518660
SN  - 1664-3224
N1  - 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.
VL  - 10
IS  - Art. 1864
SP  - 1
EP  - 15
PB  - Frontiers Media
CY  - Lausanne
ER  -