The immunology of influenza virus-associated bacterial pneumonia

Abstract

Infection with influenza virus has been a significant cause of morbidity and mortality for more than a hundred years. Severe disease and increased mortality often results from bacterial super-infection of patients with influenza virus infection. Preceding influenza infection alters the host's innate and adaptive immune responses, allowing increased susceptibility to secondary bacterial pneumonia. Recent advances in the field have helped to define how influenza alters the immune response to bacteria through the dysregulation of phagocytes, antimicrobial peptides, and lymphocytes. Viral-induced interferons play a key role in altering the phenotype of the immune response. Potential genetic modifiers of disease will help to define additional immunologic mechanisms that predispose to viral, bacterial super-infection with the overarching goal of developing effective therapeutic strategies to prevent and treat disease.

Figure 1

Chest radiographs of a child with influenza A H1N1 super-infected with methicillin-resistant Staphylococcus aureus. The window of vulnerability to secondary bacterial super-infection typically occurs typically one week post-influenza.

Figure 2

Preceding influenza attenuates innate host defense against secondary bacterial infection. In the context of bacterial infection alone, alveolar macrophages (Mac) recognize pathogens via pattern recognition receptors initiating an inflammatory cascade. Cytokines, antimicrobial peptides (AMPs), and reactive oxygen species (ROS) are generated by macrophages, recruited neutrophils, and the lung epithelium resulting in pathogen clearance. Preceding influenza (IAV) results in impaired macrophage and neutrophil killing of bacteria and decreased extracellular mediators (AMPs).

Figure 3

Influenza infection results in inhibition of Type 17 immunity in the lung. Bacterial infection induces robust IL-17, IL-22, and TNF-α production in the lung. This process mediates inflammation and antimicrobial host defense. In the context of preceding influenza (IAV), type I IFNs inhibit Type 17 immunity by attenuating IL-1β and IL-23 production by macrophages and dendritic cells. IL-17A and IL-22 production by γδ and CD4+ T cells is markedly reduced resulting in impaired host defense against bacterial challenge.