UC blood infection with clinical strains of Mycobacterium tuberculosis: a novel model

Abstract

Use of unrelated cord blood transplantation (UCBT) is increasing, yet high rates of mortality secondary to infection remain a problem. We investigated the utility of using umbilical cord blood (UCB) as a model to study a naive cell population challenged by Mycobacterium tuberculosis. Mononuclear cells were isolated from nine UCB samples and infected with each of four distinct strains of M. tuberculosis. The isolates used were two highly transmissible clinical strains, the virulent laboratory strain H37Rv and a unique strain isolated from only one case (i.e. non-virulent). CFU were assessed at 3 h post-infection (day 0) and at day 7 to generate growth curves. Viability of the mononuclear cells was assessed prior to infection, 3 h post-infection and at days 3, 5 and 7 post-infection. IFN-gamma and TNF-alpha levels were determined at 24 h post-infection. All three of the virulent strains demonstrated rapid growth in UCB cells that was significantly faster than the growth rate observed for the non-virulent unique isolate. There was no significant decrease in UCB cell viability after the 7-day incubation period regardless of infecting isolate. UCB cells secreted IFN-gamma in response to infection, with no significant difference related to infection with different isolates. However, there was a significant increase in the amount of TNF-alpha elicited following infection with the non-virulent isolate compared with the virulent isolates. These results show that UCB can be used as a model to study infection, hopefully leading to new therapies for neonates and UCBT recipients.