The influence of murine cytomegalovirus infection on susceptibility to mycobacterial infection.
Li S., Hutchings C., Korompis M., De Voss C., Ateere A., Satti I., Klenerman P., McShane H., Stylianou E.
Cytomegalovirus (CMV) infection has been associated with an increased risk of tuberculosis, but the underlying mechanisms remain unclear. Here, we used the murine CMV (MCMV), a virus genetically and biologically related to human CMV, to interrogate potential mechanisms. MCMV-infected macrophages showed reduced expression of CD80, CD86, and MHC class II, decreased phagocytosis of mycobacteria, and enhanced mycobacterial killing compared with MCMV-uninfected macrophages. Splenocytes from MCMV-infected mice better controlled mycobacterial growth ex vivo than those from MCMV-uninfected mice. However, mice infected with MCMV and subsequently challenged intranasally with mycobacteria were not more susceptible to mycobacterial infection in vivo, irrespective of the tested MCMV infection route, the interval between infections, or Bacillus Calmette-Guérin (BCG) vaccination status. These findings offer insights into how prior CMV infection may modulate host responses to mycobacteria. Further studies using more virulent mycobacterial strains, more susceptible mouse models, and varied infection timings are needed to extend these results.