Understanding the development of tuberculous granulomas: insights into host protection and pathogenesis, a review in humans and animals.

Granulomas, organized aggregates of immune cells which form in response to (), are characteristic but not exclusive of tuberculosis (TB). Despite existing investigations on TB granulomas, the determinants that differentiate host-protective granulomas from granulomas that contribute to TB pathogenesis are often disputed. Thus, the goal of this narrative review is to help clarify the existing literature on such determinants.

Nontuberculous Mycobacterial Pulmonary Disease: Patients, Principles, and Prospects.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing in incidence globally and challenging to manage. The 2020 multisociety treatment guideline and the 2022 consensus recommendations provide comprehensive evidence-based guides to manage pulmonary diseases caused by the most common NTM. However, with >190 different NTM species that may require different multidrug regimens for treatment, the breadth and complexity of NTM-PD remain daunting for both patients and clinicians.

Analysis of alpha-1-antitrypsin (AAT)-regulated, glucocorticoid receptor-dependent genes in macrophages reveals a novel host defense function of AAT.

Alpha-1-antitrypsin (AAT) plays a homeostatic role in attenuating excessive inflammation and augmenting host defense against microbes. We demonstrated previously that AAT binds to the glucocorticoid receptor (GR) resulting in significant anti-inflammatory and antimycobacterial consequences in macrophages. Our current investigation aims to uncover AAT-regulated genes that rely on GR in macrophages.

A narrative review of the controversy on the risk of mycobacterial infections with immune checkpoint inhibitor use: does Goldilocks have the answer?

Background And Objective: Immune checkpoint inhibitors (ICIs) have revolutionized oncologic treatment. Whether ICIs increase susceptibility to or provide protection against mycobacterial infections remains controversial. The objective of this narrative review is to summarize the literature on the link between ICI use and mycobacterial infections-tuberculosis and non-tuberculous mycobacterial (NTM) infections-and to critically discuss evidence linking ICIs with mycobacterial infections, the possible confounders, and, if indeed the ICIs predispose to such infections, the potential mechanisms of how this may occur.

The Inhibition of Serine Proteases by Serpins Is Augmented by Negatively Charged Heparin: A Concise Review of Some Clinically Relevant Interactions.

Serine proteases are members of a large family of hydrolytic enzymes in which a particular serine residue in the active site performs an essential role as a nucleophile, which is required for their proteolytic cleavage function. The array of functions performed by serine proteases is vast and includes, among others, the following: the ability to fight infections; the activation of blood coagulation or blood clot lysis systems; the activation of digestive enzymes; and reproduction. Serine protease activity is highly regulated by multiple families of protease inhibitors, known collectively as the SERine Protease INhibitor (SERPIN).

Manifestations and management of Sjögren's disease.

Sjögren's disease is a heterogeneous autoimmune disorder that may be associated with systemic manifestations such as pulmonary or articular involvement. Systemic complications have prognostic implications and need to be identified and managed in a timely manner. Treatment should be tailored to the type and severity of organ involvement, ideally based on multidisciplinary evaluation.

Hawaiian Volcanic Ash, an Airborne Fomite for Nontuberculous Mycobacteria.

Nontuberculous mycobacteria (NTM) are environmentally acquired opportunistic pathogens that can cause chronic lung disease. Within the U.S.

and evidence that cigarette smoke-exposed T regulatory cells impair host immunity against .

Introduction: A strong epidemiologic link exists between cigarette smoke (CS) exposure and susceptibility to tuberculosis (TB). Macrophage and murine studies showed that CS and nicotine impair host-protective immune cells against infection. While CS and nicotine may activate T regulatory cells (Tregs), little is known about how CS may affect these immunosuppressive cells with infection.

Complete genome assembly of Hawai'i environmental nontuberculous mycobacteria reveals unexpected co-isolation with methylobacteria.

Nontuberculous mycobacteria (NTM) are ubiquitous environmental opportunistic pathogens that can cause chronic lung disease. Within the United States, Hawai'i has the highest incidence of NTM lung disease, though the precise reasons are yet to be fully elucidated. One possibility is the high prevalence of NTM in the Hawai'i environment acting as a potential reservoir for opportunistic NTM infections.

Immunological and metabolic characterization of environmental Mycobacterium chimaera infection in a murine model.

Mycobacterium chimaera causes pulmonary disease, but little is known of gradations in isolate virulence. Previously, 17 M. chimaera isolates were screened for survival in THP1 macrophages.

Alpha-1-antitrypsin antagonizes COVID-19: a review of the epidemiology, molecular mechanisms, and clinical evidence.

Alpha-1-antitrypsin (AAT), a serine protease inhibitor (serpin), is increasingly recognized to inhibit SARS-CoV-2 infection and counter many of the pathogenic mechanisms of COVID-19. Herein, we reviewed the epidemiologic evidence, the molecular mechanisms, and the clinical evidence that support this paradigm. As background to our discussion, we first examined the basic mechanism of SARS-CoV-2 infection and contend that despite the availability of vaccines and anti-viral agents, COVID-19 remains problematic due to viral evolution.

Fulminant pulmonary tuberculosis in a previously healthy young woman from the Marshall Islands: Potential risk factors.

A 19-year-old woman originally from the Republic of the Marshall Islands presented with diffuse pneumonia and acute hypoxemic respiratory failure. She dies one month into her hospitalization but the diagnosis of pulmonary tuberculosis (TB) was not made until one day before her demise. A contact investigation screened a total of 155 persons with 36 (23%) found to have latent TB infection and seven (4.

Microvascular significance of TGF-β axis activation in COVID-19.

As 2023 approaches, the COVID-19 pandemic has killed millions. While vaccines have been a crucial intervention, only a few effective medications exist for prevention and treatment of COVID-19 in breakthrough cases or in unvaccinated or immunocompromised patients. SARS-CoV-2 displays early and unusual features of micro-thrombosis and immune dysregulation that target endothelial beds of the lungs, skin, and other organs.

Image-guided percutaneous biopsy and pathological diagnosis in atypical tuberculous spondylitis: a case series and clinical outcomes.

Background: Tuberculous spondylitis can be difficult to distinguish from alternative spinal pathologies such as malignancy, particularly if the imaging features are not typical. Biopsy and histopathological analysis are facilitative to the early and accurate diagnosis of atypical tuberculous spondylitis and the clinical management. The purpose of this study is to describe some of the atypical imaging features of tuberculous spondylitis diagnosed by image-guided percutaneous biopsy, as well as associated treatment outcomes.

Ancillary treatment of patients with lung disease due to non-tuberculous mycobacteria: a narrative review.

Background And Objective: Non-tuberculous mycobacterial lung disease (NTM-LD) manifests with bronchiectasis, inflammatory bronchiolitis, nodules, and/or cavitation. Bronchiectasis is characterized by permanently dilated airways wherein mucus accumulates, creating a vicious cycle of chronic injurious inflammation and recurrent infections. While antibiotics are an important part of the treatment of NTM-LD, airway clearance techniques to mitigate this pathogenic mechanism of bronchiectasis as well as other ancillary measures are also important components of NTM-LD treatment.

α1-Antitrypsin Binds to the Glucocorticoid Receptor with Anti-Inflammatory and Antimycobacterial Significance in Macrophages.

α1-Antitrypsin (AAT), a serine protease inhibitor, is the third most abundant protein in plasma. Although the best-known function of AAT is irreversible inhibition of elastase, AAT is an acute-phase reactant and is increasingly recognized to have a panoply of other functions, including as an anti-inflammatory mediator and a host-protective molecule against various pathogens. Although a canonical receptor for AAT has not been identified, AAT can be internalized into the cytoplasm and is known to affect gene regulation.

: It's Complex.

() is an opportunistic pathogen usually colonizing abnormal lung airways and is often seen in patients with cystic fibrosis. Currently, there is no vaccine available for in clinical development. The treatment of -related pulmonary diseases is peculiar due to intrinsic resistance to several commonly used antibiotics.

Characterization of Immune Cells From the Lungs of Patients With Chronic Non-Tuberculous Mycobacteria or Infection.

Little is known of the lung cellular immunophenotypes in patients with non-tuberculous mycobacterial lung disease (NTM-LD). Flow-cytometric analyses for the major myeloid and lymphoid cell subsets were performed in less- and more-diseased areas of surgically resected lungs from six patients with NTM-LD and two with lung disease (-LD). Lymphocytes, comprised mainly of NK cells, CD4 and CD8 T cells, and B cells, accounted for ~60% of all leukocytes, with greater prevalence of T and B cells in more-diseased areas.

Low Body Mass Index at Treatment Initiation and Rifampicin-Resistant Tuberculosis Treatment Outcomes: An Individual Participant Data Meta-Analysis.

Background: The impact of low body mass index (BMI) at initiation of rifampicin-resistant tuberculosis (RR-TB) treatment on outcomes is uncertain. We evaluated the association between BMI at RR-TB treatment initiation and end-of-treatment outcomes.

Methods: We performed an individual participant data meta-analysis of adults aged ≥18 years with RR-TB whose BMI was documented at treatment initiation.