Unexpected similarities in cellular responses to bacterial and viral invasion

An innate immune response has developed as a rapid and regulated defense mechanism in which the recognition of an invading pathogenic organism can occur on binding to a specific viral receptor or Toll-like receptor (TLR) that can recognize the conserved patterns of the proteins, lipoproteins, double-stranded RNA (dsRNA), or unmethylated CpG DNA (1).

As an early response to infection, cells induce a profile of the early inflammatory genes, including antiviral cytokines and chemokines. Two families of the transcriptional factors play a major role in the transcriptional activation of these genes: a well characterized family of NF-κB factors and a newly emerging family of IFN regulatory factors (IRFs). The IRFs play a critical role in the induction of type I IFN and chemokine genes and genes mediating antiviral, antibacterial, and inflammatory responses. Three of these IRFs, IRF-3, IRF-5, and IRF-7, function as direct transducers of virus-mediated signaling (2). In uninfected cells, these IRFs reside in the cytoplasm, whereas in infected cells they are phosphorylated on serine residues in the carboxyl-terminal region of the polypeptide and are transported to the nucleus. In infected cells, ubiquitously expressed IRF-3 mediates induction of IFN-B genes and some of the IFN-induced genes, whereas IRF-5 and IRF-7, expression of which is limited to lymphoid cells, are required for induction of most of the IFN-A genes. Recent data indicate that the binding of a ligand, dsRNA to TLR-3 and lipopolysaccharide (LPS) to TLR-4, also activates IRF-3 and IRF-7 (3). Binding of LPS to TLR-4 (Fig. 1) activates signaling events not only through the MyD88 adapter but also by the MyD88-independent pathway. This second pathway is mediated by two adapters named TRIF and TRAM that activate IRF-3 and induce IFN-β (3, 4). In contrast to TLR-4, TLR-3 does not associate with MyD88, MAL, and TRAM, and thus …