Clinical latency and reactivation of AIDS-related mycobacterial infections.
The immune mechanisms associated with the evolution from latent to clinically active mycobacterial coinfection in human immunodeficiency virus type 1 (HIV-1)-infected humans remain poorly understood. Previous work has demonstrated that macaques infected with simian immunodeficiency virus (SIVmac) can develop persistent Mycobacterium bovis BCG coinfection and a fatal SIV-related tuberculosis-like disease by 4 months after BCG inoculation. In the present study, SIVmac-infected monkeys that developed clinically quiescent mycobacterial infection after BCG inoculation were followed prospectively for the reactivation of the BCG and the development of SIV-related tuberculosis-like disease. The development of clinically latent BCG coinfection in these SIVmac-infected monkeys was characterized by a change from high to undetectable levels of bacterial organisms, with or without measurable BCG mRNA expression in lymph node cells. The reactivation of clinically latent BCG coinfection and development of SIV-related tuberculosis-like disease were then observed in these SIVmac-BCG-coinfected monkeys during a 21-month period of follow-up. The reactivation of SIV-related tuberculosis-like disease in these animals coincided with a severe depletion of CD4 T cells and a loss of BCG-specific T-cell responses. Interestingly, bacterial superantigen challenge of the SIVmac-BCG-coinfected monkeys resulted in an up-regulation of clinically latent BCG coinfection, suggesting that infection with superantigen-producing microbes may increase the susceptibility of individuals to the reactivation of AIDS-related mycobacterial coinfection. Thus, reactivation of latent mycobacterial infections in HIV-1-infected individuals may result from a loss of T-cell immunity or from a superimposed further compromise of the immune system.
Shen
Yun
Y
Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois, Chicago, IL, USA.
Shen
Ling
L
Sehgal
Prabhat
P
Huang
Dan
D
Qiu
Liyou
L
Du
George
G
Letvin
Norman L
NL
Chen
Zheng W
ZW
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D000818:Animals; D018791:CD4 Lymphocyte Count; D006801:Humans; D008253:Macaca mulatta; D008254:Macaca nemestrina; D009163:Mycobacterium bovis / Q000472:pathogenicity*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014376:Tuberculosis / Q000150:complications / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*
D018089:Superantigens