Cytomegalovirus infection is a risk factor for tuberculosis disease in infants

Tools for Assessing the Protective Efficacy of TB Vaccines in Humans: in vitro Mycobacterial Growth Inhibition Predicts Outcome of in vivo Mycobacterial Infection

“…Several studies suggest a protective role for hypoxia during M.tb infection (60,61). However, hypoxia is amplified as a result of inflammation, and a hypoxia-dominated expression profile may be indicative of 'too much' inflammation, resulting in suppression of the beneficial T cell response and consistent with recent reports linking high levels of immune activation with risk of TB disease (62)(63)(64). Alternatively, hypoxia may be directly limiting the cellular response in these volunteers; indeed HIF-1α has been shown in some studies to inhibit the differentiation, proliferation and IFN-γ/IL-2 production of Th1 cells (65)(66)(67).…”

Reduced Ebola vaccine responses in CMV+ young adults is associated with expansion of CD57+KLRG1+ T cells

“…Second, there is likely an effect of age (or length of CMV carriage). In contrast to studies in older adults, in which CMV has often been negatively associated with immune responses ( Derhovanessian et al, 2013 , 2014 ), various studies in children and infants have demonstrated no effect or positive effects of CMV carriage ( Miles et al, 2008 ; Holder et al, 2010 ; van den Heuvel et al, 2016 ), although CMV has also been associated with an increased risk of tuberculosis disease in infants ( Müller et al, 2019 ). In particular, the expansion of terminally differentiated CD57 + CD27 − CD28 − CD4 + T cells in CMV + adults is not always apparent in CMV + infants, even when CD57 − CD27 − CD28 − CD4 + T cells are expanded ( Miles et al, 2008 ).…”

Regulation of the human NK cell compartment by pathogens and vaccines

“…These cells are potent producers of both IL‐22 and IFN‐γ that are implicated, respectively, in tissue repair and inflammation 65 . Whether these NK cell expansions rely on prior infection or co‐infection with other pathogens is unknown although there is some evidence that the course of tuberculosis can be modulated by HCMV co‐infection 66,67 …”

“…65 Whether these NK cell expansions rely on prior infection or co-infection with other pathogens is unknown although there is some evidence that the course of tuberculosis can be modulated by HCMV co-infection. 66,67 EMERGING PATHOGENS AND NK CELLS As described above, an abundance of experimental and observational studies suggests a role for infections, especially repeated or persistent parasite or viral infections, in gradual and extensive NK cell differentiation. Furthermore, studies of emerging pathogens are providing additional insights into the relative impacts of innate and adaptive immune pathways in inducing NK cell differentiation.…”