Macrophage memories of early-life injury drive neonatal nociceptive priming.

The developing peripheral nervous and immune systems are functionally distinct from those of adults. These systems are vulnerable to early-life injury, which influences outcomes related to nociception following subsequent injury later in life (i.e.

Utilization of a zinc reporter reveals the complexities of fungal sensing of metal deprivation.

is a dimorphic fungal pathogen acquired via inhalation of soil-resident spores. Upon exposure to mammalian body temperatures, these fungal elements transform into yeasts that reside primarily within phagocytes. Macrophages (MΦ) provide a permissive environment for fungal replication until T cell-dependent immunity is engaged.

Utilization of a zinc reporter reveals the complexities of fungal sensing of metal deprivation.

Unlabelled: is a dimorphic fungal pathogen acquired via inhalation of soil-resident spores. Upon exposure to mammalian body temperatures, these fungal elements transform into yeasts that reside primarily within phagocytes. Macrophages (MΦ) provide a permissive environment for fungal replication until T cell-dependent immunity is engaged.

Macrophage epigenetic memories of early life injury drive neonatal nociceptive priming.

The developing peripheral nervous and immune systems are functionally distinct from adults. These systems are vulnerable to early life injury, which influences outcomes related to nociception following subsequent injury later in life (neonatal nociceptive priming). The underpinnings of this phenomenon are largely unknown, although previous work indicates that macrophages are epigenetically trained by inflammation and injury.

Pro-Inflammatory Alterations of Circulating Monocytes in Latent Tuberculosis Infection.

Background: Latent tuberculosis infection (LTBI) has been associated with increased cardiovascular risk. We investigated the activation and pro-inflammatory profile of monocytes in individuals with LTBI and their association with coronary artery disease (CAD).

Methods: Individuals 40-70 years old in Lima, Peru, underwent QuantiFERON-TB testing to define LTBI, completed a coronary computed tomography angiography to evaluate CAD, and provided blood for monocyte profiling using flow cytometry.

They shall not grow mold: Soldiers of innate and adaptive immunity to fungi.

Fungi are ubiquitous commensals, seasoned predators, and important agents of emerging infectious diseases [1]. The immune system assumes the essential responsibility for responding intelligently to the presence of known and novel fungi to maintain host health. In this Review, we describe the immune responses to pathogenic fungi and the varied array of fungal agents confronting the vertebrate host within the broader context of fungal and animal evolution.

Polyfunctional Antigen Specific CD4+ T cell Responses in Patients With Human Immunodeficiency Virus/AIDS and Histoplasmosis Immune Reconstitution Inflammatory Syndrome.

In the combination antiretroviral era, there are limited data regarding the pathogenesis of histoplasmosis immune reconstitution inflammatory syndrome (IRIS) in people with human immunodeficiency virus (HIV). We immunologically characterized 10 cases of histoplasmosis, 4 of whom developed histoplasmosis IRIS. CD4+ T cells in histoplasmosis IRIS demonstrated a significant polyfunctional cytokine response to histoplasma antigen.

Notch regulates Histoplasma capsulatum clearance in mouse lungs during innate and adaptive immune response phases in primary infection.

The clearance of the pathogenic fungus, Histoplasma capsulatum, requires cooperation between innate and adaptive immunity. Since this organism is inhaled, lung macrophages and dendritic cells (DCs) are the first lines of defense. Moreover, DCs act as APCs to drive the education of type 1 Th cells to produce IFNγ, which contributes to the final elimination of H.

Restraint of Fumarate Accrual by HIF-1α Preserves miR-27a-Mediated Limitation of Interleukin 10 during Infection of Macrophages by Histoplasma capsulatum.

Hypoxia-inducible factor 1α (HIF-1α) regulates the immunometabolic phenotype of macrophages, including the orchestration of inflammatory and antimicrobial processes. Macrophages deficient in HIF-1α produce excessive quantities of the anti-inflammatory cytokine interleukin 10 (IL-10) during infection with the intracellular fungal pathogen Histoplasma capsulatum (R. A.

A metabolic inhibitor arms macrophages to kill intracellular fungal pathogens by manipulating zinc homeostasis.

Macrophages deploy numerous strategies to combat invasion by microbes. One tactic is to restrict acquisition of diverse nutrients, including trace metals, a process termed nutritional immunity. Intracellular pathogens adapt to a resource-poor environment by marshaling mechanisms to harvest nutrients.

Adipocyte inflammation and pathogenesis of viral pneumonias: an overlooked contribution.

Epidemiological evidence establishes obesity as an independent risk factor for increased susceptibility and severity to viral respiratory pneumonias associated with H1N1 influenza and SARS-CoV-2 pandemics. Given the global obesity prevalence, a better understanding of the mechanisms behind obese susceptibility to infection is imperative. Altered immune cell metabolism and function are often perceived as a key causative factor of dysregulated inflammation.

Regulation of the Mitochondrion-Fatty Acid Axis for the Metabolic Reprogramming of Chlamydia trachomatis during Treatment with β-Lactam Antimicrobials.

Infection with the obligate intracellular bacterium is the most common bacterial sexually transmitted disease worldwide. Since no vaccine is available to date, antimicrobial therapy is the only alternative in infection. However, changes in chlamydial replicative activity and the occurrence of chlamydial persistence caused by diverse stimuli have been proven to impair treatment effectiveness.

Bacille-Calmette-Guérin Infection Aggravates Atherosclerosis.

Tuberculosis has been associated with increased risk of atherosclerotic cardiovascular disease. To examine whether mycobacterial infection exacerbates atherosclerosis development in experimental conditions, we infected low-density lipoprotein receptor knockout () mice with Bacille-Calmette-Guérin (BCG), an attenuated strain of the complex. Twelve-week old male mice were infected with BCG (0.

CD4CTLs in Fibrosing Mediastinitis Linked to .

Although fibrotic disorders are frequently assumed to be linked to T cells, quantitative tissue interrogation studies have rarely been performed to establish this link and certainly many fibrotic diseases do not fall within the type 2/allergic disease spectrum. We have previously linked two human autoimmune fibrotic diseases, IgG4-related disease and systemic sclerosis, to the clonal expansion and lesional accumulation of CD4CTLs. In both these diseases T cell accumulation was found to be sparse.

GM-CSF and IL-33 Orchestrate Polynucleation and Polyploidy of Resident Murine Alveolar Macrophages in a Murine Model of Allergic Asthma.

Allergic asthma is a chronical pulmonary disease with high prevalence. It manifests as a maladaptive immune response to common airborne allergens and is characterized by airway hyperresponsiveness, eosinophilia, type 2 cytokine-associated inflammation, and mucus overproduction. Alveolar macrophages (AMs), although contributing to lung homeostasis and tolerance to allergens at steady state, have attracted less attention compared to professional antigen-presenting and adaptive immune cells in their contributions.

Crosstalk Between Autophagy and Hypoxia-Inducible Factor-1α in Antifungal Immunity.

Modern medicine is challenged by several potentially severe fungal pathogens such as , or . Though not all fungal pathogens have evolved as primary pathogens, opportunistic pathogens can still cause fatal infections in immuno-compromised patients. After infection with these fungi, the ingestion and clearance by innate immune cells is an important part of the host immune response.

IL-10-producing Tfh cells accumulate with age and link inflammation with age-related immune suppression.

Aging results in profound immune dysfunction, resulting in the decline of vaccine responsiveness previously attributed to irreversible defects in the immune system. In addition to increased interleukin-6 (IL-6), we found aged mice exhibit increased systemic IL-10 that requires forkhead box P3-negative (FoxP3), but not FoxP3, CD4T cells. Most IL-10-producing cells manifested a T follicular helper (Tfh) phenotype and required the Tfh cytokines IL-6 and IL-21 for their accrual, so we refer to them as Tfh10 cells.

Metabolism of Gluconeogenic Substrates by an Intracellular Fungal Pathogen Circumvents Nutritional Limitations within Macrophages.

Microbial pathogens exploit host nutrients to proliferate and cause disease. Intracellular pathogens, particularly those exclusively living in the phagosome such as , must adapt and acquire nutrients within the nutrient-limited phagosomal environment. In this study, we investigated which host nutrients could be utilized by as carbon sources to proliferate within macrophages.

Type I Interferons Rule with an Iron Fist.

Pathogens rely on nutrient assimilation, particularly essential metal incorporation, to successfully survive in the host. In this issue of Cell Host & Microbe, Riedelberger et al. (2020) convincingly demonstrate that type I interferons (IFNs-I) promote dysregulation of iron homeostasis in macrophages upon infection with Candida glabrata and exacerbate infection.

Macrophage Function in the Pathogenesis of Non-alcoholic Fatty Liver Disease: The Mac Attack.

Obesity is a prevalent predisposing factor to non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease in the developed world. NAFLD spectrum of disease involves progression from steatosis (NAFL), to steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Despite clinical and public health significance, current FDA approved therapies for NAFLD are lacking in part due to insufficient understanding of pathogenic mechanisms driving disease progression.

Metallothionein 3 Controls the Phenotype and Metabolic Programming of Alternatively Activated Macrophages.

Alternatively activated (M2) macrophages promote wound healing but weaken antimicrobial defenses. The mechanisms that enforce macrophage divergence and dictate the phenotypic and metabolic characteristics of M2 macrophages remain elusive. We show that alternative activation with interleukin (IL)-4 induces expression of metallothionein 3 (MT3) that regulates macrophage polarization and function.

The intersection of host and fungus through the zinc lens.

In this review, we summarize data regarding the influence of zinc on host defenses to human pathogenic fungi and how the fungus acquires zinc to sustain biological functions. Mammals have evolved several extracellular and intracellular mechanisms to withhold zinc from the fungus. Specific immune cells release zinc binding proteins such as calprotectin to capture the metal and deny it to the fungus.

The HIF-1α/LC3-II Axis Impacts Fungal Immunity in Human Macrophages.

The fungal pathogen causes a spectrum of disease, ranging from local pulmonary infection to disseminated disease. The organism seeks residence in macrophages, which are permissive for its survival. Hypoxia-inducible factor 1α (HIF-1α), a principal regulator of innate immunity to pathogens, is necessary for macrophage-mediated immunity to in mice.

Aeroallergens Exacerbate Infection.

Allergens such as house dust mites (HDM) and papain induce strong Th2 responses, including elevated IL-4, IL-5, and IL-13 and marked eosinophilia in the airways. is a dimorphic fungal pathogen that induces a strong Th1 response marked by IFN-γ and TNF-α production, leading to rapid clearance in nonimmunocompromised hosts. Th1 responses are generally dominant and overwhelm the Th2 response when stimuli for both are present, although there are instances when Th2 stimuli downregulate a Th1 response.