Latent viral infection alters the immune architecture of the lung

Human cytomegalovirus (HCMV) is ubiquitous virus infecting most humans and developing persistent latent infections. HCMV reactivation occurs in ~33% of immune-competent patients during critical illness associated with doubled risk of mortality. In many persistent infections Myeloid derived suppressor cells (MDSC) cause T cell dysfunction, creating an immunosuppressive microenvironment. We hypothesized that latent CMV infection induces MDSC, perhaps contributing the impairment of host resolution of infection and thus latency. BALB/c mice were infected with 1×106 PFU of Smith strain murine CMV and lung mononuclear cells (LMNC) were cultured ex vivo or stained for surface markers and analyzed by ELISA or FACS. During latency, we observed a change in frequency (million/gm of lung tissue) of cell subsets such as marked reduction of CD4+T and B cells, increased CD8+T cells and significant increase in NK cells compared to naive mice. Interestingly, the percentage of MDSC was unchanged at 2 weeks, but was significantly reduced at12 weeks post infection (p.i.). Both IL-6 and TNF-α were elevated in unstimulated or LPS, ConA stimulated LMNC at 2 and 12 weeks p.i. conferring the risk of lung pathology under critical illness. Our findings suggest that during the transition from acute to latent infection, persistent pro-inflammatory lung immune environment is associated with reduced MDSC. Longitudinal studies are underway to explore the role of MDSC in lungs of latently infected mice.