HIV Skews a Balanced Mtb-Specific Th17 Response in Latent Tuberculosis Subjects to a Pro-inflammatory Profile Independent of Viral Load

Abstract

Highlights d Chronic HIV infection selectively impairs Mtb-specific effector cytokine responses d Chronic HIV infection augments Mtb-specific proinflammatory Th17 responses d HIV-induced changes in Mtb-specific cells are independent of viral load and MIP-1b d ART/ATT restore anti-inflammatory and dampen proinflammatory Th17 responses

A century of BCG: Impact on tuberculosis control and beyond

“…Several studies have highlighted the contribution of IL‐17‐ and IL‐22‐producing CD4 + T cell subsets toward protective anti‐mycobacterial immunity, 90,91 while others have demonstrated reduced frequencies of Th17 cells and low serum IL‐17 levels in TB patients compared to LTBI subjects to be associated with high mortality in TB patients 92‐94 . Consistent with these reports, recent studies from our laboratory have provided further evidence in this aspect, whereby IL‐10 + regulatory Th17 cells enriched in latent TB subjects were skewed toward IFN‐γ + pro‐inflammatory Th17 cells in active TB and HIV‐infected patients; however, a balanced Th17 response was restored following anti‐tubercular and anti‐retroviral therapy, respectively 95,96 . Additionally, a correlation between the inhibition of Th17 responses and progression from infection to active TB was revealed by transcriptional and clinical analyses of healthy South African adolescents 97 .…”

“…[92][93][94] Consistent with these reports, recent studies from our laboratory have provided further evidence in this aspect, whereby IL-10 + regulatory Th17 cells enriched in latent TB subjects were skewed toward IFNγ + pro-inflammatory Th17 cells in active TB and HIV-infected patients; however, a balanced Th17 response was restored following antitubercular and anti-retroviral therapy, respectively. 95,96 Additionally, a correlation between the inhibition of Th17 responses and progression from infection to active TB was revealed by transcriptional and clinical analyses of healthy South African adolescents. 97 Subsequently, Th17 cells have steadily emerged as key players in vaccine-induced protection against TB, 98,99 even in the absence of IFNγ.…”

Host‐directed therapy to combat mycobacterial infections*

“…A large proportion of human Mtb-specific CD4 Th1-cells expresses CCR6 and co-produces IFNγ/IL-17, often depicted as Th1* or Th1-17 cells, and being associated with LTBI suggest their importance in protection against active TB 143. However, IL-17 responses during TB need to be carefully regulated to prevent neutrophil-driven lung pathology, which is mediated by regulatory T-cells as well as so-called regulatory CD4 Th17-cells that coproduce IL-17 and IL-10 144. In case of disbalanced Th17 responses Th2-cytokine, impaired mycobacterial control by human macrophages and enhanced the proportion of regulatory T-cells in vitro.…”

Viral Load and CD4+ Markers as Determinants of Tuberculosis Coinfection Among People Living with HIV/AIDS in Papua Indonesia

“…7 However, the annual risk of active TB in people with TB-HIV coinfection is 5-15%. 6 It is estimated that PLHIV is 18 (15)(16)(17)(18)(19)(20)(21) times more at risk of developing TB than people without HIV. 1 TB-HIV coinfection also has a high case fatality rate and a lifetime risk.…”

“…These conditions can increase the chance of reactivation of dormant TB bacteria. 16 The pathogenesis of TB infection among PLHIV is directly related to the decline of the immune system, especially a decrease in CD4 + T lymphocytes. Thereby it reduces the immunological response to M. tuberculosis.…”