title: 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 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.
authors.affiliation: Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27101.
authors.forename: Lance K
authors.initials: LK
authors.lastname: Blevins
authors.affiliation: Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27101.
authors.forename: John T
authors.initials: JT
authors.lastname: Wren
authors.affiliation: Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27101.
authors.forename: Beth C
authors.initials: BC
authors.lastname: Holbrook
authors.affiliation: Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27101.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Hayward
authors.affiliation: Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27101.
authors.forename: W Edward
authors.initials: WE
authors.lastname: Swords
authors.affiliation: Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27101.
authors.forename: Griffith D
authors.initials: GD
authors.lastname: Parks
authors.affiliation: Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27101 marthaam@wakehealth.edu.
authors.forename: Martha A
authors.initials: MA
authors.lastname: Alexander-Miller
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D058491:Bacterial Load; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D060085:Coinfection; D005260:Female; D007111:Immunity, Cellular; D056747:Immunomodulation; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D012720:Severity of Illness Index; D013296:Streptococcus pneumoniae / Q000276:immunology; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism; D019562:Viral Load
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma