Necrosis of host cells and survival of pathogens following iron overload in an in vitro model of co-infection with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis.

Mycobacterium tuberculosis, human immunodeficiency virus (HIV) and iron overload (dietary/hereditary) are very common in sub-Saharan Africa. The requirement for iron as a crucial factor for cellular processes is well established, as are the disadvantages of excess iron in the system. Mycobacterium tuberculosis and HIV are believed to have a reciprocal effect on each another. An in vitro model was evaluated where chronically HIV-infected cells were secondarily exposed to M. tuberculosis in the presence of iron overload. Co-infection alone caused cell type-specific reductions in host cell viability, more than doubled the number of viral particles and stimulated bacterial viability. Excess iron (in addition to co-infection) further decreased cell viability, with a marked increase in necrosis (rather than apoptosis) of cells, and was also found to enhance both HIV (26%; P<0.01) and M. tuberculosis (47%; P<0.01) replication. Chelation of excess iron with deferoxamine abrogated the enhanced replication of the pathogens, with a marginal restoration in host cell viability. These findings demonstrate that (i) increased levels of iron in HIV-infected patients secondarily co-infected with M. tuberculosis elevate viral replication, which could lead to rapid disease progression, and (ii) iron chelation may serve as a means to slow/decelerate these processes.