27 February 2012
HIV and Mycobacterium tuberculosis interact to worsen each infection and drive AIDS morbidity and mortality in many regions, yet the mechanisms behind this interaction are not well understood. This review article by HIV and TB experts at Sweden’s Karolinska Institute and Lund University focuses on the “immunological events that may accelerate the development of one of the two diseases in the presence of the co-infecting organism.”
HIV, these authors write, is the most powerful factor predisposing vulnerable populations to TB infection and progression to active disease. HIV raises the risk of latent TB reactivation 20-fold. TB in turn is the most common cause of AIDS-related death.
These investigators also review animal models that may illuminate interactions between the two infections and detail knowledge gaps as well as future studies that should be planned to prevent the two infections.
Specifically, the article covers the following topics:
— Development of standardized in vitro and in vivo models for coinfection studies
— Interactions and receptor signaling in dendritic cells
— HIV/M tuberculosis-specific T- and B- cell responses
— Role of memory T cells in maintaining latent infection and of regulatory T cells in disease outbreak
— Effector mechanisms of T cells involved in protection against TB
— Role of antimicrobial peptides in cytolytic T cells
— Regulation of T-cell differentiation during coinfection
— Immunologic synapses
— Interactions between T cells and antigen-presenting cells
— Mathematical modeling and simulation of T-, B-, and NK-cell repertoires
— Mechanisms of HIV–TB interactions in immune reconstitution inflammatory syndrome (IRIS)
— Role of individual HIV/M tuberculosis antigens/molecules in immunopathology
— Effect on immune response in infected individuals after vaccination with TB and/or HIV vaccine candidates
Ultimately, these experts believe, the best way to fight both infections would be a single vaccine active against both of them. One approach would be a combined TB/HIV vaccine using a recombinant BCG vaccine as a vehicle for mycobacterial and HIV antigens. Such a combination vaccine would be optimal if given at mucosal sites.
The authors acknowledge that developing such a vaccine requires much further research into the biology of coinfection with the two pathogens using in vitro systems, animal models, clinical studies, and eventually vaccine trials.
Source: Andrzej Pawlowski, Marianne Jansson, Markus Sköld, Martin E. Rottenberg, Gunilla Källenius. Tuberculosis and HIV co-infection. PLoS Pathogens. 2012; 8(2): e1002464.
Complete article provided by PLoS Pathogens, an open-access journal