Coinfection with Streptococcus pneumoniae negatively modulates the size and composition of the ongoing
Lance K Blevins1, John T Wren1, Beth C Holbrook1
1Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27101.
Abstract:
Infection with influenza A virus 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. In this study, we show that infection of mice with influenza virus, followed by the noninvasive 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 that 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 IFN-γ exhibited a decreased potential for coproduction of TNF-α. Reduced cytokine production was directly correlated with a decrease in the level of mRNA. Negative regulation of cells in the mediastinal lymph node was minimal compared with that present in the lung, supporting a model of selective regulation in the tissue harboring high pathogen burden. These results show that entry of a coinfecting pathogen can have profound immunoregulatory effects on an ongoing immune response. Together, these findings reveal a novel dynamic interplay between concurrently infecting pathogens and the adaptive immune system.
Insights
Influenza A virus infection impairs the lung CD8(+) T cell response to a subsequent Streptococcus pneumoniae infection. This immune suppression in coinfected mice increases disease severity and mortality.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Influenza A virus infection can increase susceptibility to secondary bacterial infections, particularly Streptococcus pneumoniae.
- The lung environment is significantly altered post-infection, potentially modulating immune responses.
Purpose of the Study:
- To investigate the immunoregulatory effects of coinfection with influenza A virus and Streptococcus pneumoniae on virus-specific CD8(+) T cell responses in the lung.
- To determine the impact of these immunoregulatory effects on disease outcomes.
Main Methods:
- Mice were infected with influenza A virus followed by Streptococcus pneumoniae (strain EF3030).
- Virus-specific CD8(+) T cell responses in the lung and mediastinal lymph nodes were analyzed.
- Adoptive transfer studies were performed to assess the contribution of reduced CD8(+) T cells to disease.
- Cytokine production (IFN-γ, TNF-α) and mRNA levels in immune cells were measured.
Main Results:
- Coinfection significantly decreased the virus-specific CD8(+) T cell response in the lung.
- Reduced CD8(+) T cell numbers correlated with increased mortality and decreased cytokine production in surviving cells.
- Impaired IFN-γ and TNF-α coproduction was observed in coinfected animals.
- Selective immune regulation occurred primarily in the lung, with minimal effects in the mediastinal lymph node.
Conclusions:
- Subsequent bacterial infection profoundly suppresses ongoing antiviral CD8(+) T cell immunity in the lung.
- This immunoregulatory effect contributes to increased disease severity during coinfection.
- A dynamic interplay exists between concurrently infecting pathogens and the adaptive immune system, highlighting novel regulatory mechanisms.
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