Coinfection with Streptococcus pneumoniae Negatively Modulates the Size and Composition of the Ongoing Influenza-Specific CD8+ T Cell Response

Abstract

Infection with influenza A virus (IAV) can lead to increased susceptibility to subsequent bacterial infection, often with Streptococcus pneumoniae. Given the substantial modification of the lung environment that occurs following pathogen infection, there is significant potential for modulation of immune responses. Here we show that coinfection of mice with influenza virus followed by the non-invasive EF3030 strain of Streptococcus pneumoniae leads to a significant decrease in the virus specific CD8+ T cell response in the lung. Adoptive transfer studies suggest this reduction contributes to disease in coinfected animals. The reduced number of lung effector cells in coinfected animals was associated with increased death as well as a reduction in cytokine production in surviving cells. Further, cells that retained the ability to produce interferon γ exhibited a decreased potential for co-production of tumor necrosis factor α. Reduced cytokine production was directly correlated with a decrease in the level of mRNA. Negative regulation of cells in the mediastinal lymph node (MLN) was minimal compared to that present in the lung, supporting a model of negative regulation in the tissue harboring high pathogen burden. These results elucidate a new aspect of immune regulation as a result of entry of a coinfecting pathogen, modulation of ongoing adaptive immune responses in the lung. These findings reveal a novel dynamic interplay between concurrently infecting pathogens and the adaptive immune system.

Influenza A Virus Infection Predisposes Hosts to Secondary Infection with Different Streptococcus pneumoniae Serotypes with Similar Outcome but Serotype-Specific Manifestation

“…This clearly demonstrated that acute IAV infection has devastating effects on antipneumococcal host defenses that are independent of the IPD potential of the coinfecting pneumococcal strain. Strikingly, even the carrier strain 19F caused severe disease and mortality following coinfection at a dose that was nonlethal in the absence of IAV infection in our model as well as in previously described studies (29,33). IAV infection has been shown to also support the development of otitis media by 19F (34,35).…”

Host‐pathogen kinetics during influenza infection and coinfection: insights from predictive modeling

“…Moreover, infections with different pathogens species can affect the number of T cells and may lead to repeated influenza virus infections. For example, CD4 + and CD8 + T cells decrease significantly during influenza coinfection with bacteria . How this impacts viral clearances and shapes later responses is unknown.…”

Virus-Bacteria Interactions: An Emerging Topic in Human Infection

“…By infecting and replicating within cells originally primed for defense, the host response is severely hindered (for a thorough review of the immune system subversion of respiratory or enteric viruses see [6] or [9], respectively). Once again, influenza has also been documented to promote this type of dynamic as well, as the viruses deplete alveolar macrophages, impairing bacterial clearance of the pathogenic S. pneumonia [54,55]. Furthermore, the virus alters the Toll-like receptor pathways, resulting in decreased neutrophil attraction, which in turn increases the attachment of bacterial cells onto host epithelium [7].…”