Publikationsdatenbank

In vivo Neutralization of Pro-inflammatory Cytokines During Secondary Streptococcus pneumoniae Infection Post Influenza A Virus Infection (2019)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Sharma-Chawla, Niharika

Stegemann-Koniszewski, Sabine

Christen, Henrike

Boehme, Julia D.

Kershaw, Olivia (WE 12)

Schreiber, Jens

Guzmán, Carlos A.

Bruder, Dunja

Hernandez-Vargas, Esteban A.

Quelle

Frontiers in immunology

Bandzählung: 10

Seiten: Article 1864

ISSN: 1664-3224

Sprache

Englisch

Verweise

URL (Volltext): https://www.frontiersin.org/articles/10.3389/fimmu.2019.01864/full

DOI: 10.3389/fimmu.2019.01864

Pubmed: 31474978

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.