Received: 9 October 2017
Accepted: 18 January 2018
Alterations in natural killer and dendritic cell subsets in
individuals with HIV-associated neurotuberculosis
Manjunatha M. Venkataswamy
Department of Neurovirology, National
Institute of Mental Health and Neurosciences
(NIMHANS), Bangalore, India
Department of Neurology, National Institute
of Mental Health and Neurosciences
(NIMHANS), Bangalore, India
Anita Desai, Department of Neurovirology,
National Institute of Mental Health and
Neurosciences (NIMHANS), 560029
One of the commonest HIV-associated opportunistic infections of the central nervous
system is neurotuberculosis. Interaction between HIV, Mycobacterium tuberculosis and host
immune system in co-infected individuals may result in altered frequencies of immune cells,
thereby modulating dissemination and disease progression. We examined the frequencies
of natural killer (NK) cell and dendritic cell (DC) subsets in HIV infected individuals with
neurotuberculosis (HIVNTB) as compared to individuals with HIV associated systemic TB
(HIVSTB), asymptomatic HIV, non-HIV NTB, non-HIV STB, and healthy controls. Peripheral
blood mononuclear cells (PBMC) were stained with fluorochrome-conjugated monoclonal
antibodies- Lineage cocktail (containing CD3, CD14, CD19, and CD20), HLA-DR, CD16,
CD56, CD11c, and CD123, fixed with 2% paraformaldehyde and analyzed on the flow
cytometer. The pDCs were significantly reduced in all HIV infected groups, with a marked
reduction in HIVNTB cases as compared to healthy controls. While the CD56
cell subset displayed a significant increase in frequency in all three HIV infected groups
compared the three HIV negative groups, the CD56
subset was significantly
lower in frequency in the HIVNTB compared to healthy controls. The decreased
frequencies of plasmacytoid DCs and cytotoxic NK cells, which are crucial for innate
immune defence against HIV, may result in ineffective virus control and lead to an
exacerbated course of disease in HIVNTB individuals.
dendritic cell, HIV/AIDS, innate immunity, natural Killer cell, tuberculosis
One of the commonest opportunistic infections (OIs) in HIV infected
individuals in developing countries, including India, is tuberculosis (TB).
The recent WHO report states that of the 2.8 million TB infections in
India in 2015, around 4% were among HIV positive individuals.
There is a vast body of evidence indicating dysregulated immune
responses in HIV infection. The modulation of host immunity in TB is
also well established. When these two diseases converge, the
consequences are devastating,
resulting in significant morbidity and
mortality. Studies have shown that the risk of developing active TB
increases in individuals with HIV.
Active TB disease also causes an
exacerbated course of HIV infection.
HIV infection has brought with it increasing cases of extrapulmo-
involving multiple organs with poor-formed granulomas.
The likelihood of HIV-infected individuals developing TB of the CNS is
five times more than those negative for HIV.
HIV alters the immune
response to M. tuberculosis in multiple ways.
Lower CD4 T cell counts
are associated with higher rate of TB reactivation, especially CD4 T cell
counts <200 μL which result in increased susceptibility to dissemi-
nated TB. Well-defined granulomas are lacking in these patients,
resulting in ineffective containment of the infection.
J Med Virol. 2018;90:899–906. wileyonlinelibrary.com/journal/jmv © 2018 Wiley Periodicals, Inc.