Altered Signal Transduction in the Immune Response to Influenza Virus and S. pneumoniae or S. aureus Co-Infections

Abstract

Influenza virus is a well-known respiratory pathogen, which still leads to many severe pulmonary infections in the human population every year. Morbidity and mortality rates are further increased if virus infection coincides with co-infections or superinfections caused by bacteria such as Streptococcus pneumoniae (S. pneumoniae) and Staphylococcus aureus (S. aureus). This enhanced pathogenicity is due to complex interactions between the different pathogens and the host and its immune system and is mainly governed by altered intracellular signaling processes. In this review, we summarize the recent findings regarding the innate and adaptive immune responses during co-infection with influenza virus and S. pneumoniae or S. aureus, describing the signaling pathways involved and how these interactions influence disease outcomes.

Keywords: S. aureus; S. pneumoniae; immune response; influenza virus.

Figure 1

The complement system and its role in pathogen clearance. Schematic overview of the activation of the classical, the lectin and the alternative signaling pathway, leading to the formation of the membrane attack complex (MAC). Interference of the different pathogens with the complement system pathways is indicated by red inhibition arrows. This figure was created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://smart.servier.com (accessed on 11 February 2021).

Figure 2

Schematic depiction of the most prominent PRR-mediated signaling events in co-infections with influenza viruses and S. pneumoniae or S. aureus. Detection of extra- and intracellular PAMPs induces the expression of type I IFN and various cytokines and chemokines, resulting in pro- and anti-pathogen responses and the recruitment of immune cells. This figure was created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://smart.servier.com (accessed on 11 February 2021).

Figure 3

Changes in immune cell recruitment and activation in influenza virus co-infection with S. pneumoniae or S. aureus. This figure was created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://smart.servier.com (accessed on 11 February 2021).