How does bacterial-viral co-infection impact anti-viral immunity?
Majority of murine lymphocytic choriomeningitis virus (LCMV) infection studies are conducted in specific pathogen free environments. In reality, viral infections occur with other bacterial and/or fungal infections. The effect of CMV on bacterial co-infections has been extensively studied, however the reverse has not.
To shed light on how bacterial infection affects LCMV induced immunity, researchers infected mice with E.coli a day post LCMV infection. Straub et al., showed that E.coli results in significantly lower proportions of LCMV-specific T cells and higher LCMV burden compared with controls. This anti-LCMV immunity was mediated by indirect activation of NK cells by toll-like receptor ligands such as lipopolysaccharides (LPS from bacteria), resulting in suppression of T cells by NK cells in a perforin independent manner.
LPS induces innate cells to produce pro-inflammatory cytokines such as IL-15, a cytokine important for NK cell activation and survival. To determine if IL-15 is responsible for indirect activation of NK cells, researchers used monoclonal antibodies to block IL-15 activity in LCMV-E.coli co-infected mice. Interestingly, despite decreased proportions of NK cells due IL-15 depletion, NK cell mediated anti-viral activity was not affected. Illustrating that LPS-induced NK activity during LCMV-E.coli co-infection is also independent of IL-15 signalling. Finally, they showed that LPS-induced NK mediated killing of LCMV-specific T cells is not due to the activity of NK receptors NKG2D and NCR1, receptors previously shown to be important for killing T cells in LCMV (only) infected mice.
In summary, the study by Straub et al., demonstrates how bacterial co-infections can negatively impact anti-LCMV immunity and viral control. Where TLR stimulation leads to NK cell mediated suppression of virus specific T cells and LCMV control in a NKG2D and NCR1 independent manner.
Journal Article: Straub et al., 2018. Bacterial coinfection restrains antiviral CD8 T-cell response via LPS-induced inhibitory NK cells. Nature Communications
Article by Cheleka AM Mpande