Tuberculosis is the leading infectious cause of death worldwide, and HIV-1 the best recognized risk factor for active TB. This review focuses on immune complex formation; the interplay of type I and II interferon signaling; and T-cell activation in HIV–TB pathogenesis.
Circulating immune complexes and complement, and Fcγ signaling in whole blood act as early markers of TB disease in HIV-1-infected persons. HIV-1 is associated with a type I interferon response in whole blood, reducing the specificity of TB biomarkers dependent on type I and II interferon genes. Type I and type II interferons are implicated in both protection and TB disease, a protective outcome may depend on modulating these pathways. Whilst M. tuberculosis-specific CD4 T cells are preferentially depleted during HIV-1 infection, activation markers on M. tuberculosis-specific CD4 T cells, in particular HLA-DR, reflect immune activation and have promise as biomarkers of M. tuberculosis disease activity in individuals with HIV-1.
TB pathogenesis in HIV-1 involves a complex interaction of underlying activation of both the innate and adaptive immune systems. Further research is required to understand whether biomarkers of activation could be used to predict or quantify TB disease in the context of HIV-1 infection.
aWellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine
bDivision of Medical Microbiology, Department of Pathology, University of Cape Town, Observatory, South Africa
cRadcliffe Department of Medicine, University of Oxford
dDepartment of Medicine, Imperial College London, London, United Kingdom
eWalter and Eliza Hall Institute of Medical Research
fDivision of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia
gThe Francis Crick Institute, London, United Kingdom
Correspondence to Patrick J. Howlett, Mb Chb, Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa. E-mail: email@example.com