Flu Virus Attenuates Memory Clearance of Pneumococcus via IFN-γ-Dependent Th17 and Independent Antibody Mechanisms

Bacterial coinfection is a major cause of influenza-associated mortality. Most people have experienced infections with bacterial pathogens commonly associated with influenza A virus (IAV) coinfection before IAV exposure; however, bacterial clearance through the immunological memory response (IMR) in coinfected patients is inefficient, suggesting that the IMR to bacteria is impaired during IAV infection. Adoptive transfer of CD4(+) T cells from mice that had experienced bacterial infection into IAV-infected mice revealed that memory protection against bacteria was weakened in the latter. Additionally, memory Th17 cell responses were impaired due to an IFN-γ-dependent reduction in Th17 cell proliferation and delayed migration of CD4(+) T cells into the lungs. A bacterium-specific antibody-mediated memory response was also substantially reduced in coinfected mice, independently of IFN-γ. These findings provide additional perspectives on the pathogenesis of coinfection and suggest additional strategies for the treatment of defective antibacterial immunity and the design of bacterial vaccines against coinfection.