Transcriptome immune-regulatory differences between leprosy patients and type 1 reaction patients, before onset of symptoms.

Leprosy is a chronic disease of the skin and peripheral nerves caused by Mycobacterium leprae. A major public health and clinical problem are leprosy reactions, which are inflammatory episodes that often contribute to nerve damage and disability. Type I reversal reactions (T1R) can occur after microbiological cure of leprosy and affect up to 50% of leprosy patients.

Latent Tuberculosis Infection Is Associated with an Enrichment of Short-Chain Fatty Acid-Producing Bacteria in the Stool of Women Living with HIV.

Latent tuberculosis infection (LTBI) is common in people living with HIV (PLHIV) in high-TB-burden settings. Active TB is associated with specific stool taxa; however, little is known about the stool microbiota and LTBI in PLHIV. We characterised the stool microbiota of PLHIV with [interferon- release assay (IGRA)- and tuberculin skin test (TST)-positive] or without (IGRA- and TST-negative) LTBI ( = 25 per group).

Dynamics of pulmonary mucosal cytotoxic CD8 T-cells in people living with HIV under suppressive antiretroviral therapy.

Background: Despite the success of antiretroviral therapy (ART), people living with HIV (PLWH) suffer from a high burden of pulmonary diseases, even after accounting for their smoking status. Cytotoxic CD8 T-cells are likely implicated in this phenomenon and may act as a double-edged sword. While being essential in viral infection control, their hyperactivation can also contribute to lung mucosal tissue damage.

Latent tuberculosis infection is associated with an enrichment of short chain fatty acid producing bacteria in the stool of women living with HIV.

Background: Latent tuberculosis infection (LTBI) is common in people living with HIV (PLHIV) in high TB burden settings. Active TB is associated with specific stool taxa; however, little is known about the stool microbiota and LTBI, including in PLHIV.

Method: Within a parent study that recruited adult females with HIV from Cape Town, South Africa into predefined age categories (18-25, 35-60 years), we characterised the stool microbiota of those with [interferon-γ release assay (IGRA)- and tuberculin skin test (TST)-positive] or without (IGRA- and TST- negative) LTBI (n=25 per group).

Mycobacterium tuberculosis resisters despite HIV exhibit activated T cells and macrophages in their pulmonary alveoli.

To understand natural resistance to ( ) infection, we studied people living with HIV (PLWH) in an area of high transmission. Given that alveolar leukocytes may contribute to this resistance, we performed single cell RNA-sequencing of bronchoalveolar lavage cells, unstimulated or stimulated with . We obtained high quality cells for 7 participants who were TST & IGRA positive (called LTBI) and 6 who were persistently TST & IGRA negative (called resisters).

Neutrophil extracellular trap formation and gene programs distinguish TST/IGRA sensitization outcomes among Mycobacterium tuberculosis exposed persons living with HIV.

Persons living with HIV (PLWH) have an increased risk for tuberculosis (TB). After prolonged and repeated exposure, some PLWH never develop TB and show no evidence of immune sensitization to Mycobacterium tuberculosis (Mtb) as defined by persistently negative tuberculin skin tests (TST) and interferon gamma release assays (IGRA). This group has been identified and defined as HIV+ persistently TB, tuberculin and IGRA negative (HITTIN).

Pet Protection Orders for Domestic Violence Survivors: Are They Being Used?

This study examines if and how pet protection orders have been used by domestic violence survivors in the 36 states and the District of Columbia in which they have been enacted. A review of court websites determined if there was a specific item to include a pet in the temporary and/or final protection order. In addition, individual court administrators were contacted in various states to determine if statistics were available on the number of pet protection orders issued.

Deep ulcers are associated with increased C-reactive protein in active ulcerative colitis.

Background: Increased C-reactive protein (CRP) is used to diagnose and predict response to treatment in acute severe ulcerative colitis (UC).

Aims: To investigate the connection between CRP elevation and deep ulcers in UC.

Methods: Patients with active UC were enrolled in a multicenter prospective cohort and a retrospective cohort of consecutive patients undergoing colectomy from 2012 to 2019.

Allele-dependent interaction of LRRK2 and NOD2 in leprosy.

Leprosy, caused by Mycobacterium leprae, rarely affects children younger than 5 years. Here, we studied a multiplex leprosy family that included monozygotic twins aged 22 months suffering from paucibacillary leprosy. Whole genome sequencing identified three amino acid mutations previously associated with Crohn's disease and Parkinson's disease as candidate variants for early onset leprosy: LRRK2 N551K, R1398H and NOD2 R702W.

Human alveolar macrophage metabolism is compromised during infection.

Pulmonary macrophages have two distinct ontogenies: long-lived embryonically-seeded alveolar macrophages (AM) and bone marrow-derived macrophages (BMDM). Here, we show that after infection with a virulent strain of (H37Rv), primary murine AM exhibit a unique transcriptomic signature characterized by metabolic reprogramming distinct from conventional BMDM. In contrast to BMDM, AM failed to shift from oxidative phosphorylation (OXPHOS) to glycolysis and consequently were unable to control infection with an avirulent strain (H37Ra).

The bacterial virulence factor NleA undergoes host-mediated O-linked glycosylation.

Enterohaemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) are gastrointestinal pathogens responsible for severe diarrheal illness. EHEC and EPEC form "attaching and effacing" lesions during colonization and, upon adherence, inject proteins directly into host intestinal cells via the type III secretion system (T3SS). Injected bacterial proteins have a variety of functions but generally alter host cell biology to favor survival and/or replication of the pathogen.

Deep resequencing identifies candidate functional genes in leprosy GWAS loci.

Leprosy is the second most prevalent mycobacterial disease globally. Despite the existence of an effective therapy, leprosy incidence has consistently remained above 200,000 cases per year since 2010. Numerous host genetic factors have been identified for leprosy that contribute to the persistently high case numbers.

Alveolar macrophages from persons living with HIV show impaired epigenetic response to Mycobacterium tuberculosis.

Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is often the result of recent infection with Mycobacterium tuberculosis (M. tuberculosis) followed by rapid progression to disease.

Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to .

Human genetic control is thought to affect a considerable part of the outcome of infection with (). Most of us deal with the pathogen by containment (associated with clinical "latency") or sterilization, but tragically millions each year do not. After decades of studies on host genetic susceptibility to infection, genetic variation has been discovered to play a role in tuberculous immunoreactivity and tuberculosis (TB) disease.

Perspectives for systems biology in the management of tuberculosis.

Standardised management of tuberculosis may soon be replaced by individualised, precision medicine-guided therapies informed with knowledge provided by the field of systems biology. Systems biology is a rapidly expanding field of computational and mathematical analysis and modelling of complex biological systems that can provide insights into mechanisms underlying tuberculosis, identify novel biomarkers, and help to optimise prevention, diagnosis and treatment of disease. These advances are critically important in the context of the evolving epidemic of drug-resistant tuberculosis.

Genome-wide association study of resistance to Mycobacterium tuberculosis infection identifies a locus at 10q26.2 in three distinct populations.

The natural history of tuberculosis (TB) is characterized by a large inter-individual outcome variability after exposure to Mycobacterium tuberculosis. Specifically, some highly exposed individuals remain resistant to M. tuberculosis infection, as inferred by tuberculin skin test (TST) or interferon-gamma release assays (IGRAs).

Lessons From Bacille Calmette-Guérin for SARS-CoV-2 Vaccine Candidates.

Developers of severe acute respiratory syndrome coronavirus 2 vaccines should consider some of the lessons from a "new" vaccine introduced in 1921, namely bacille Calmette-Guérin.

Cell-free DNA tissues of origin by methylation profiling reveals significant cell, tissue, and organ-specific injury related to COVID-19 severity.

Background: Coronavirus disease 2019 (COVID-19) primarily affects the lungs, but evidence of systemic disease with multi-organ involvement is emerging. Here, we developed a blood test to broadly quantify cell-, tissue-, and organ-specific injury due to COVID-19.

Methods: Our test leverages genome-wide methylation profiling of circulating cell-free DNA in plasma.