B cell heterogeneity in human tuberculosis highlights compartment-specific phenotype and functional roles.

B cells are important in tuberculosis (TB) immunity, but their role in the human lung is understudied. Here, we characterize B cells from lung tissue and matched blood of patients with TB and found they are decreased in the blood and increased in the lungs, consistent with recruitment to infected tissue, where they are located in granuloma associated lymphoid tissue. Flow cytometry and transcriptomics identify multiple B cell populations in the lung, including those associated with tissue resident memory, germinal centers, antibody secretion, proinflammatory atypical B cells, and regulatory B cells, some of which are expanded in TB disease.

High-parameter phenotypic characterization reveals a subset of human Th17 cells that preferentially produce IL-17 against antigen.

Background: Interleukin-17-producing CD4 T cells contribute to the control of () infection in humans; whether infection with human immunodeficiency virus (HIV) disproportionately affects distinct Th17-cell subsets that respond to is incompletely defined.

Methods: We performed high-definition characterization of circulating -specific Th17 cells by spectral flow cytometry in people with latent TB and treated HIV (HIV-ART). We also measured kynurenine pathway activity by liquid chromatography-mass spectrometry (LC/MS) on plasma and tested the hypothesis that tryptophan catabolism influences Th17-cell frequencies in this context.

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.

High-parameter phenotypic characterization reveals a subset of human Th17 cells that preferentially produce IL17 against antigen.

Background: Interleukin 17 producing CD4 T cells contribute to the control of infection in humans; whether infection with Human Immunodeficiency Virus (HIV) disproportionately affects distinct Th17 cell subsets that respond to is incompletely defined.

Methods: We performed high-definition characterization of circulating -specific Th17 cells by spectral flow cytometry in people with latent TB and treated HIV (HIV-ART). We also measured kynurenine pathway activity by LC/MS on plasma and tested the hypothesis that tryptophan catabolism influences Th17 cell frequencies in this context.

Do vaginal microbicides reduce the risk of HIV acquisition in women?

Currently, no single HIV prevention method meets the needs of all people at risk of infection and a range of options are needed for individuals to protect themselves and to curb the HIV epidemic. Many people living with HIV or at risk for HIV infection in low and middle-income countries do not have access to prevention, treatment and care, and there is still no cure. Despite large preventive efforts, HIV acquisition rates remain unacceptably high and transmission mainly occurs through heterosexual intercourse, where women are significantly more vulnerable to infection than men.

Finding antigens for TB vaccines: the good, the bad and the useless.

Prospective, longitudinal clinical studies incorporating high-throughput, single-cell analyses could identify which bacterial antigens to include in TB vaccines — and which to avoid.

The Road to Elimination: Current State of Schistosomiasis Research and Progress Towards the End Game.

The new WHO Roadmap for Neglected Tropical Diseases targets the global elimination of schistosomiasis as a public health problem. To date, control strategies have focused on effective diagnostics, mass drug administration, complementary and integrative public health interventions. Non-mammalian intermediate hosts and other vertebrates promote transmission of schistosomiasis and have been utilized as experimental model systems.

Performance Evaluation of Lateral Flow Assays for Coronavirus Disease-19 Serology.

The coronavirus disease of 2019 (COVID-19) pandemic, caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has undoubtedly resulted in significant morbidities, mortalities, and economic disruptions across the globe. Affordable and scalable tools to monitor the transmission dynamics of the SARS-CoV-2 virus and the longevity of induced antibodies will be paramount to monitor and control the pandemic as multiple waves continue to rage in many countries. Serologic assays detect humoral responses to the virus, to determine seroprevalence in target populations, or induction of antibodies at the individual level following either natural infection or vaccination.

A Framework to Identify Antigen-Expanded T Cell Receptor Clusters Within Complex Repertoires.

Common approaches for monitoring T cell responses are limited in their multiplexity and sensitivity. In contrast, deep sequencing of the T Cell Receptor (TCR) repertoire provides a global view that is limited only in terms of theoretical sensitivity due to the depth of available sampling; however, the assignment of antigen specificities within TCR repertoires has become a bottleneck. This study combines antigen-driven expansion, deep TCR sequencing, and a novel analysis framework to show that homologous 'Clusters of Expanded TCRs (CETs)' can be confidently identified without cell isolation, and assigned to antigen against a background of non-specific clones.

Acquired Clinical Immunity to Malaria in Nonhuman Primates Coinfected with and Parasites.

Naturally acquired immunity to malaria develops over several years and can be compromised by concomitant infections. This study explored the influence of chronic schistosomiasis on clinical outcome and immunity to repeated malaria infection. Two groups of baboons ( = 8 each), were infected with Schistosoma mansoni cercariae to establish chronic infections.

Repeated infection in humans drives the clonal expansion of an adaptive γδ T cell repertoire.

Repeated infections drive the development of clinical immunity to malaria in humans; however, the immunological mechanisms that underpin this response are only partially understood. We investigated the impact of repeated infections on human γδ T cells in the context of natural infection in Malian children and adults, as well as serial controlled human malaria infection (CHMI) of U.S.

Tissue-resident-like CD4+ T cells secreting IL-17 control Mycobacterium tuberculosis in the human lung.

T cell immunity is essential for the control of tuberculosis (TB), an important disease of the lung, and is generally studied in humans using peripheral blood cells. Mounting evidence, however, indicates that tissue-resident memory T cells (Trms) are superior at controlling many pathogens, including Mycobacterium tuberculosis (M. tuberculosis), and can be quite different from those in circulation.

Unbiased Profiling Reveals Compartmentalization of Unconventional T-Cells Within the Intestinal Mucosa Irrespective of HIV Infection.

The intestinal mucosa is enriched for unconventional T-cells, including mucosal associated invariant T-cells (MAIT), invariant natural killer T-cells (iNKT) and γδ T-cells. These cells are activated by bacterial metabolites, lipid antigens and cytokines, and are important for intestinal barrier integrity. The loss of gut homeostasis observed in HIV infection is central to disease pathogenesis, and studies have highlighted impairment of particular unconventional T-cell subsets within a specific gut compartment.

Anti-PD-1 immunotherapy leads to tuberculosis reactivation via dysregulation of TNF-α.

Previously, we developed a 3-dimensional cell culture model of human tuberculosis (TB) and demonstrated its potential to interrogate the host-pathogen interaction (Tezera et al., 2017a). Here, we use the model to investigate mechanisms whereby immune checkpoint therapy for cancer paradoxically activates TB infection.

Differential skewing of donor-unrestricted and γδ T cell repertoires in tuberculosis-infected human lungs.

Unconventional T cells that recognize mycobacterial antigens are of great interest as potential vaccine targets against tuberculosis (TB). This includes donor-unrestricted T cells (DURTs), such as mucosa-associated invariant T cells (MAITs), CD1-restricted T cells, and γδ T cells. We exploited the distinctive nature of DURTs and γδ T cell receptors (TCRs) to investigate the involvement of these T cells during TB in the human lung by global TCR sequencing.

Publisher Correction: Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Plasma IL-5 but Not CXCL13 Correlates With Neutralization Breadth in HIV-Infected Children.

Children may be the optimal target for HIV vaccine development as they generate substantially more frequent and more potent broadly HIV neutralizing antibodies (bnAbs) than adults. Development of a biomarker that correlates with neutralization breadth in this group could function as a powerful tool to facilitate the development of an HIV vaccine. Previously, we observed that this preferential ability in HIV-infected children over adults to generate bnAbs is associated with an enrichment of circulating follicular helper T-cells (T) with an effector phenotype, and the presence of IL-21 secreting HIV-specific T within lymphoid tissue germinal centers (GC).

Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis.

Tuberculosis is the leading cause of death by an infectious disease worldwide. However, the involvement of innate lymphoid cells (ILCs) in immune responses to infection with Mycobacterium tuberculosis (Mtb) is unknown. Here we show that circulating subsets of ILCs are depleted from the blood of participants with pulmonary tuberculosis and restored upon treatment.

Lung Tissue Resident Memory T-Cells in the Immune Response to .

Despite widespread BCG vaccination and effective anti-TB drugs, Tuberculosis (TB) remains the leading cause of death from an infectious agent worldwide. Several recent publications give reasons to be optimistic about the possibility of a more effective vaccine, but the only full-scale clinical trial conducted failed to show protection above BCG. The immunogenicity of vaccines in humans is primarily evaluated by the systemic immune responses they generate, despite the fact that a correlation between these responses and protection from TB disease has not been demonstrated.

Major TCR Repertoire Perturbation by Immunodominant HLA-B44:03-Restricted CMV-Specific T Cells.

Lack of disease during chronic human cytomegalovirus (CMV) infection depends on the maintenance of a high-frequency CMV-specific T cell response. The composition of the T cell receptor (TCR) repertoire underlying this response remains poorly characterised, especially within African populations in which CMV is endemic from infancy. Here we focus on the immunodominant CD8+ T cell response to the immediate-early 2 (IE-2)-derived epitope NEGVKAAW (NW8) restricted by HLA-B44:03, a highly prevalent response in African populations, which in some subjects represents >10% of the circulating CD8+ T cells.