Novel mechanism of immunosuppression by influenza virus haemagglutinin: selective suppression of interleukin 12 p35 transcription in murine bone marrow-derived dendritic cells

Influenza virus infection predisposes patients to bacterial superinfection, but the underlying immunological mechanisms remain poorly understood. This study investigated whether influenza hemagglutinin (HA), the major surface antigen, modulates immune dendritic cell responses to bacterial lipopolysaccharide (LPS). Using murine bone marrow-derived dendritic cells (BMDCs), researchers found that HA selectively suppresses LPS-induced interleukin-12 (IL-12) p70 production in a dose-dependent manner. Importantly, this suppression is specific to IL-12, with no effect on other inflammatory cytokines or chemokines. The mechanism operates at the transcriptional level, with HA selectively inhibiting p35 subunit mRNA expression while leaving p40 subunit expression unchanged. Suppression is independent of IL-10 or interferon signaling. The findings were confirmed in vivo, where HA administration reduced LPS-induced IL-12 and interferon-gamma production in mice. These results suggest a novel immunosuppressive mechanism by which influenza virus may increase host susceptibility to bacterial infections through targeted disruption of IL-12 p35 gene transcription in dendritic cells.

Key findings

• Influenza hemagglutinin selectively suppresses LPS-induced IL-12 p70 production by dendritic cells in a dose-dependent manner
• Suppression occurs at the transcriptional level with selective inhibition of the p35 subunit while p40 expression remains unchanged
• The suppressive effect is independent of IL-10 or interferon signaling and can be reversed by anti-HA antibodies
• In vivo experiments confirm that HA administration reduces both IL-12 p70 and interferon-gamma production in mice
• This selective p35 inhibition represents a novel mechanism that may explain increased susceptibility to bacterial superinfection during influenza virus infections