Rare Variable Antigens induce predominant Th17 responses in human infection.

CD4 T cells are essential for immunity to (), and emerging evidence indicates that IL-17-producing Th17 cells contribute to immunity to . While identifying protective T cell effector functions is important for TB vaccine design, T cell antigen specificity is also likely to be important. To identify antigens that induce protective immunity, we reasoned that as in other pathogens, effective immune recognition drives sequence diversity in individual antigens.

Active Tuberculosis Is Associated with Depletion of HIV-Specific CD4 and CD8 T Cells in People with HIV.

Infection with (Mtb) in people with HIV (PWH) is associated with depletion of Mtb-specific CD4 T cell responses, increased risk of progression to active tuberculosis (TB) disease, and increased immune activation. Although higher HIV viral loads have been reported in Mtb/HIV co-infection, the extent to which Mtb infection and TB disease impact the frequency and phenotype of HIV-specific T cell responses has not been well described. We enrolled a cohort of PWH in Kenya across a spectrum of Mtb infection states, including those with no evidence of Mtb infection, latent Mtb infection (LTBI), and active pulmonary TB disease, and evaluated the frequency, immune activation, and cytotoxicity phenotype of HIV-specific CD4 and CD8 T cell responses in peripheral blood by flow cytometry.

Associations of psychological inflexibility with posttraumatic stress disorder and adherence to COVID-19 control measures among refugees in Uganda: The moderating role of coping strategies.

Refugees are vulnerable to developing mental health problems. The unprecedented appearance and rapid spread of COVID-19 exacerbated this vulnerability, especially in low-income countries where refugees survive on humanitarian aid and live in congested settlements. These appalling living conditions are a stressor, making adherence to COVID-19 control measures impractical and an additional psychological strain for refugees.

Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial.

Background: Oral pre-exposure prophylaxis has been introduced in more than 70 countries, including many in sub-Saharan Africa, but women experience considerable barriers to daily pill-taking, such as stigma, judgement, and the fear of violence. Safe and effective long-acting agents for HIV prevention are needed for women. We aimed to evaluate the safety and efficacy of injectable cabotegravir compared with daily oral tenofovir diphosphate plus emtricitabine (TDF-FTC) for HIV prevention in HIV-uninfected women.

Schistosoma mansoni Infection Is Associated With a Higher Probability of Tuberculosis Disease in HIV-Infected Adults in Kenya.

Background: Helminth infections can modulate immunity to Mycobacterium tuberculosis (Mtb). However, the effect of helminths, including Schistosoma mansoni (SM), on Mtb infection outcomes is less clear. Furthermore, HIV is a known risk factor for tuberculosis (TB) disease and has been implicated in SM pathogenesis.

Adults from Kisumu, Kenya have robust γδ T cell responses to Schistosoma mansoni, which are modulated by tuberculosis.

Schistosoma mansoni (SM) is a parasitic helminth that infects over 200 million people and causes severe morbidity. It undergoes a multi-stage life cycle in human hosts and as such stimulates a stage-specific immune response. The human T cell response to SM is complex and varies throughout the life cycle of SM.

Activation-Induced Marker Expression Identifies -Specific CD4 T Cells in a Cytokine-Independent Manner in HIV-Infected Individuals with Latent Tuberculosis.

HIV infection is a significant risk factor for reactivation of latent infection (LTBI) and progression to active tuberculosis disease, yet the mechanisms whereby HIV impairs T cell immunity to have not been fully defined. Evaluation of -specific CD4 T cells is commonly based on IFN-γ production, yet increasing evidence indicates the immune response to is heterogeneous and encompasses IFN-γ-independent responses. We hypothesized that upregulation of surface activation-induced markers (AIM) would facilitate detection of human -specific CD4 T cells in a cytokine-independent manner in HIV-infected and HIV-uninfected individuals with LTBI.

Tryptophan catabolism reflects disease activity in human tuberculosis.

There is limited understanding of the role of host metabolism in the pathophysiology of human tuberculosis (TB). Using high-resolution metabolomics with an unbiased approach to metabolic pathway analysis, we discovered that the tryptophan pathway is highly regulated throughout the spectrum of TB infection and disease. This regulation is characterized by increased catabolism of tryptophan to kynurenine, which was evident not only in active TB disease but also in latent TB infection (LTBI).

Distinct Human NK Cell Phenotypes and Functional Responses to in Adults From TB Endemic and Non-endemic Regions.

(Mtb) is the causative agent of tuberculosis (TB), which leads to an estimated 1. 5 million deaths worldwide each year. Although the immune correlates of protection against Mtb infection and TB disease have not been well-defined, natural killer (NK) cells are increasingly recognized as a key component of the innate immune response to Mtb and as a link between innate and adaptive immunity.

HIV Infection Is Associated With Downregulation of BTLA Expression on -Specific CD4 T Cells in Active Tuberculosis Disease.

Nearly a quarter of the global population is infected with (Mtb), with 10 million people developing active tuberculosis (TB) annually. Co-infection with human immunodeficiency virus (HIV) has long been recognized as a significant risk factor for progression to TB disease, yet the mechanisms whereby HIV impairs T cell-mediated control of Mtb infection remain poorly defined. We hypothesized that HIV infection may promote upregulation of inhibitory receptors on Mtb-specific CD4 T cells, a mechanism that has been associated with antigen-specific T cell dysfunction in chronic infections.

A High Throughput Whole Blood Assay for Analysis of Multiple Antigen-Specific T Cell Responses in Human Infection.

Antigen-specific CD4 and CD8 T cells are important components of the immune response to , yet little information is currently known regarding how the breadth, specificity, phenotype, and function of -specific T cells correlate with infection outcome in humans. To facilitate evaluation of human -specific T cell responses targeting multiple different Ags, we sought to develop a high throughput and reproducible T cell response spectrum assay requiring low blood sample volumes. We describe here the optimization and standardization of a microtiter plate-based, diluted whole blood stimulation assay utilizing overlapping peptide pools corresponding to a functionally diverse panel of 60 Ags.