Mycobacterium tuberculosis Recall Antigens Suppress HIV-1 Replication in Anergic Donor Cells via CD8+ T Cell Expansion and Increased IL-10 Levels (original) (raw)
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The Journal of Infectious Diseases , 2020
Background. Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus (HIV) coinfection increases mortality, accelerates progression to acquired immune deficiency syndrome, and exacerbates tuberculosis disease. However, the impact of pre-existing Mtb infection on subsequent HIV infection has not been fully explored. We hypothesized that Mtb infection creates an immunological environment that influences the course of HIV infection, and we investigated whether pre-existing Mtb infection impacts the susceptibility of CD4 + T cells to HIV-1 infection. Methods. Plasma and blood CD4 + T cells isolated from HIV-negative individuals across the Mtb infection spectrum and non-Mtb-infected control individuals were analyzed for inflammation markers and T-cell phenotypes. CD4 + T cells were infected with HIV-1 in vitro and were monitored for viral replication. Results. We observed differences in proinflammatory cytokines and the relative proportion of memory T-cell subsets depending on Mtb infection status. CD4 + T cells derived from individuals with latent Mtb infection supported more efficient HIV-1 transcription , release, and replication. Enhanced HIV-1 replication correlated with higher percentages of CD4 + T EM and T TD cells. Conclusions. Pre-existing Mtb infection creates an immunological environment that reflects Mtb infection status and influences the susceptibility of CD4 + T cells to HIV-1 replication. These findings provide cellular and molecular insights into how pre-existing Mtb infection influences HIV-1 pathogenesis.
Future Virology, 2020
Accelerated tuberculosis and AIDS progression seen in HIV-1 and Mycobacterium tuberculosis (Mtb)-coinfected individuals indicates the important interaction between these syndemic pathogens. The immunological interaction between HIV-1 and Mtb has been largely defined by how the virus exacerbates tuberculosis disease pathogenesis. Understanding of the mechanisms by which pre-existing or subsequent Mtb infection may favor the replication, persistence and progression of HIV, is less characterized. We present a rationale for the critical consideration of ‘latent’ Mtb infection in HIV-1 prevention and cure strategies. In support of this position, we review evidence of the effect of Mtb infection on HIV-1 acquisition, replication and persistence. We propose that ‘latent’ Mtb infection may have considerable impact on HIV-1 pathogenesis and the continuing HIV-1 epidemic in sub-Saharan Africa.
HIV/Mtb Co-Infection: From the Amplification of Disease Pathogenesis to an “Emerging Syndemic”
Microorganisms
Human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (Mtb) are pathogens responsible for millions of new infections each year; together, they cause high morbidity and mortality worldwide. In addition, late-stage HIV infection increases the risk of developing tuberculosis (TB) by a factor of 20 in latently infected people, and even patients with controlled HIV infection on antiretroviral therapy (ART) have a fourfold increased risk of developing TB. Conversely, Mtb infection exacerbates HIV pathogenesis and increases the rate of AIDS progression. In this review, we discuss this reciprocal amplification of HIV/Mtb coinfection and how they influence each other’s pathogenesis. Elucidating the infectious cofactors that impact on pathogenesis may open doors for the design of new potential therapeutic strategies to control disease progression, especially in contexts where vaccines or the sterile clearance of pathogens are not effectively available.
Mycobacterium tuberculosisdisease associates with higher HIV-1-specific antibody responses
Mycobacterium tuberculosis(Mtb) can enhance immune responses against unrelated pathogens. Although Mtb is the most common co-infection in people living with HIV (PWH), there has been no examination of its impact on HIV-1 immune responses. Plasma neutralization and antibody dependent cellular cytotoxicity (ADCC) was compared among PWH and Mtb disease (PWH/Active Mtb) and PWH/No Mtb both prior to and after antiretroviral treatment (ART) and completion of Mtb therapy. We assessed HIV-1 sequences, total antibody quantities and isotypes, and plasma cytokine levels to ascertain mechanisms that affect humoral responses. HIV-1 neutralizing antibodies (nAbs) were broader and more potent in PWH/Active Mtb as compared to PWH/No Mtb, and nAbs increased among PWH who developed Mtb after ART initiation. ADCC was also higher in the PWH who had Mtb disease after starting ART. PWH/Active Mtb as compared to PWH/No Mtb had unique HIV-1 envelope sequence motifs associated with neutralization resistance...
Current Opinion in HIV and AIDS
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. Recent findings Circulating immune complexes and complement, and Fc 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 pathology, a protective outcome may depend on modulating these pathways. Whilst Mtb-specific CD4 T cells are preferentially depleted during HIV-1 infection, activation markers on Mtb-specific CD4 T cells, in particular HLA-DR, reflect immune activation and have promise as biomarkers of Mtb disease activity in individuals with HIV-1. Summary 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.
Pathogens, 2020
The performance of host blood-based biomarkers for tuberculosis (TB) in HIV-infected patients on antiretroviral therapy (ART) has not been fully assessed. We evaluated the immune phenotype and functionality of antigen-specific T-cell responses in HIV positive (+) participants with TB (n = 12) compared to HIV negative (−) participants with either TB (n = 9) or latent TB infection (LTBI) (n = 9). We show that the cytokine profile of Mtb-specific CD4+ T-cells in participants with TB, regardless of HIV status, was predominantly single IFN-γ or dual IFN-γ/ TNFα. Whilst ESAT-6/CFP-10 responding T-cells were predominantly of an effector memory (CD27−CD45RA−CCR7−) profile, HIV-specific T-cells were mainly of a central (CD27+CD45RA−CCR7+) and transitional memory (CD27+CD45RA+/−CCR7−) phenotype on both CD4+ and CD8+ T-cells. Using receiving operating characteristic (ROC) curve analysis, co-expression of CD38 and HLA-DR on ESAT-6/CFP-10 responding total cytokine-producing CD4+ T-cells had a hi...
Mycobacterium tuberculosis Infection Interferes with HIV Vaccination in Mice
PLoS ONE, 2012
Tuberculosis (TB) has emerged as the most prominent bacterial disease found in human immunodeficiency virus (HIV)positive individuals worldwide. Due to high prevalence of asymptomatic Mycobacterium tuberculosis (Mtb) infections, the future HIV vaccine in areas highly endemic for TB will often be administrated to individuals with an ongoing Mtb infection. The impact of concurrent Mtb infection on the immunogenicity of a HIV vaccine candidate, MultiHIV DNA/protein, was investigated in mice. We found that, depending on the vaccination route, mice infected with Mtb before the administration of the HIV vaccine showed impairment in both the magnitude and the quality of antibody and T cell responses to the vaccine components p24Gag and gp160Env. Mice infected with Mtb prior to intranasal HIV vaccination exhibited reduced p24Gag-specific serum IgG and IgA, and suppressed gp160Env-specific serum IgG as compared to respective titers in uninfected HIV-vaccinated controls. Importantly, in Mtb-infected mice that were HIV-vaccinated by the intramuscular route the virus neutralizing activity in serum was significantly decreased, relative to uninfected counterparts. In addition mice concurrently infected with Mtb had fewer p24Gag-specific IFN-c-expressing T cells and multifunctional T cells in their spleens. These results suggest that Mtb infection might interfere with the outcome of prospective HIV vaccination in humans.