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.
Traoré
Hafsatou Ndama
HN
Biochemistry Department, University of Johannesburg, Auckland Park Kingsway Campus, P.O. Box 524 Auckland Park, 2006 Johannesburg, South Africa.
Meyer
Debra
D
D017088:AIDS-Related Opportunistic Infections / Q000382:microbiology / Q000473:pathology; D002478:Cells, Cultured; D006678:HIV / Q000472:pathogenicity; D015658:HIV Infections / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D019190:Iron Overload / Q000382:microbiology* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000382:microbiology / Q000473:pathology / Q000821:virology; D009169:Mycobacterium tuberculosis; D009336:Necrosis; D014376:Tuberculosis / Q000382:microbiology / Q000473:pathology*