Influenza A viruses (IAVs) remain serious threats to public health
because of the shortage of effective means of control. Developing more
effective virus control modalities requires better understanding of
virus–host interactions. It has previously been shown that IAV induces
the production of kynurenine, which suppresses T-cell responses,
enhances pain hypersensitivity and disturbs behaviour in infected
animals. However, the regulation of kynurenine biosynthesis during IAV
infection remains elusive. Here we showed that IAV infection induced
expression of interferons (IFNs), which upregulated production
of indoleamine-2,3-dioxygenase (IDO1), which catalysed the kynurenine
biosynthesis. Furthermore, IAV attenuated the IDO1 expression and the production of kynurenine through its NS1 protein. Interestingly, inhibition of viral replication prior to IFN induction limited IDO1
expression, while inhibition after did not. Finally, we showed that
kynurenine biosynthesis was activated in macrophages in response to
other stimuli, such as influenza B virus, herpes simplex virus 1 and 2
as well as bacterial lipopolysaccharides. Thus, the tight regulation of
the kynurenine biosynthesis by host cell and, perhaps, pathogen might be
a basic signature of a wide range of host–pathogen interactions, which
should be taken into account during development of novel antiviral and
antibacterial drugs.