Fig 1.
CMV and TB immune mechanisms of host manipulation.
Immune manipulation by CMV (left-hand side), Mtb (right-hand side), and some examples of possible interactions between the 2 pathogens (centre) in a host cell. Examples of viral genes expressed during both active replication and latent infection aid CMV in avoiding viral peptides to be displayed on the surface of infected cells. Mtb manipulates cellular machinery to increase or decrease cytokine production and Mtb protein early secreted antigen (ESAT6) down-regulates presentation of mycobacterial peptides via MHC-I. CMV-derived viral IL-10 may interfere with protection against Mtb, and CMV-induced immune activation and enhanced type-I IFNs could increase risk and severity of TB disease. While interactions between CMV and Mtb may occur directly while a host cell is infected with both pathogens, alterations to the wider immunological environment by either pathogen may provide conditions conducive to pathogenesis by the other. The example of immune manipulation mechanisms shown here is not an exhaustive list. CMV, cytomegalovirus; ER, endoplasmic reticulum; IFN, interferon; IL, interleukin; MHC, xxx; Mtb, Mycobacterium tuberculosis; TAP, xxx; TB, tuberculosis; TNF, tumor necrosis factor.
Fig 2.
Conceptual framework of TB and CMV interaction in low- and high-risk children.
Conceptual framework of TB and CMV interaction in high-and low-risk children. Black arrows represent CMV infection, reactivation, or reinfection events. Red dashed lines show hypothesised CMV viral load following infection, reactivation, or reinfection events. Blue line represents IgG antibody levels to CMV. Lower risk child—immune competent children aged approximately between 4 and 15. Higher risk children—children aged less than 4 years old, immune compromised, HIV infected, older adolescent (over 15 years of age). Created with BioRender.com. CMV, cytomegalovirus; TB, tuberculosis.
Table 1.
Studies that have evaluated the interaction between TB and CMV.
Table 2.
Understanding the burden for CMV–TB interaction.
Table 3.
Understanding the underlying pathogenesis and immunology of CMV–TB interaction.
Table 4.
Understanding the clinical impact of CMV–TB interaction.
Table 5.
Interventions that might reduce the impact of CMV on TB progression from infection to disease.