Defective LAT signalosome pathology in mice mimics human IgG4-related disease at single-cell level.

Mice with a loss-of-function mutation in the LAT adaptor (LatY136F) develop an autoimmune and type 2 inflammatory disorder called defective LAT signalosome pathology (DLSP). We analyzed via single-cell omics the trajectory leading to LatY136F DLSP and the underlying CD4+ T cell diversification. T follicular helper cells, CD4+ cytotoxic T cells, activated B cells, and plasma cells were found in LatY136F spleen and lung.

Molecular mechanisms of antibiotic resistance revisited.

Antibiotic resistance is a global health emergency, with resistance detected to all antibiotics currently in clinical use and only a few novel drugs in the pipeline. Understanding the molecular mechanisms that bacteria use to resist the action of antimicrobials is critical to recognize global patterns of resistance and to improve the use of current drugs, as well as for the design of new drugs less susceptible to resistance development and novel strategies to combat resistance. In this Review, we explore recent advances in understanding how resistance genes contribute to the biology of the host, new structural details of relevant molecular events underpinning resistance, the identification of new resistance gene families and the interactions between different resistance mechanisms.

Lymphatic migration of unconventional T cells promotes site-specific immunity in distinct lymph nodes.

Lymphatic transport of molecules and migration of myeloid cells to lymph nodes (LNs) continuously inform lymphocytes on changes in drained tissues. Here, using LN transplantation, single-cell RNA-seq, spectral flow cytometry, and a transgenic mouse model for photolabeling, we showed that tissue-derived unconventional T cells (UTCs) migrate via the lymphatic route to locally draining LNs. As each tissue harbored a distinct spectrum of UTCs with locally adapted differentiation states and distinct T cell receptor repertoires, every draining LN was thus populated by a distinctive tissue-determined mix of these lymphocytes.

Viral infection engenders bona fide and bystander subsets of lung-resident memory B cells through a permissive mechanism.

Lung-resident memory B cells (MBCs) provide localized protection against reinfection in respiratory airways. Currently, the biology of these cells remains largely unexplored. Here, we combined influenza and SARS-CoV-2 infection with fluorescent-reporter mice to identify MBCs regardless of antigen specificity.

Identification of Non-classical Follicular T Cells.

Nonclassical T cells are a heterogeneous group of T lymphocytes that are activated during the early stages of infection and act as a bridge between the innate and adaptive immune system. Among them, Natural Killer T (NKT) cells have been extensively studied in the last two decades due to their unique ability to recognize foreign/self-lipid antigens in the context of CD1d, a nonclassical major histocompatibility complex molecule. In this chapter, we describe our protocols to track murine NKT cells in lymph nodes by flow cytometry and confocal microscopy.

[SARS-CoV-2 infection: implications for sexual and reproductive health. A position statement of the Asociación Española de Andrología, Medicina Sexual y Reproductiva (ASESA)].

Objective: The main objective of this revision is to summarize the current existing evidence of the potential adverse effects of SARS-CoV-2 on the male reproductive system and provide the recommendations of the Asociación Española de Andrología, Medicina Sexual y Reproductiva (ASESA) concerning the implications of COVID-19 infection in the management of male infertilty patients and testicular endocrine dysfunction.

Methods: A comprehensive systematic literature search of the databases of PubMed, Web of Science, Embase, Medline, Cochrane and MedRxiv, was carried out.

Results: The presence of orchitis as a potential complication of the infection by SARS-CoV-2 has not yet been confirmed.

Multicenter investigation on the influence of climate in penile prosthesis infection.

The purpose of this study is to investigate the relationship between inflatable penile prosthesis (IPP) infection, time of year, climate, temperature and humidity. This is a retrospective IRB-approved analysis of 211 patients at 25 institutions who underwent salvage procedure or device explant between 2001 and 2016. Patient data were compiled after an extensive review of all aspects of their electronic medical records.

O-antigen serotyping and MALDI-TOF, potentially useful tools for optimizing semi-empiric antipseudomonal treatments through the early detection of high-risk clones.

The increasing prevalence of extensively drug-resistant (XDR) Pseudomonas aeruginosa infections is due to the global spread of defined high-risk clones (HRC). Among them, ST175 is particularly frequent in Spain and France. Here, we evaluated O-antigen serotyping and MALDI-TOF as typing methods for the early identification of ST175.

Protein Kinase C-β Dictates B Cell Fate by Regulating Mitochondrial Remodeling, Metabolic Reprogramming, and Heme Biosynthesis.

PKCβ-null (Prkcb) mice are severely immunodeficient. Here we show that mice whose B cells lack PKCβ failed to form germinal centers and plasma cells, which undermined affinity maturation and antibody production in response to immunization. Moreover, these mice failed to develop plasma cells in response to viral infection.

CD1d-mediated lipid presentation by CD11c cells regulates intestinal homeostasis.

Intestinal homeostasis relies on a continuous dialogue between the commensal bacteria and the immune system. Natural killer T (NKT) cells, which recognize CD1d-restricted microbial lipids and self-lipids, contribute to the regulation of mucosal immunity, yet the mechanisms underlying their functions remain poorly understood. Here, we demonstrate that NKT cells respond to intestinal lipids and CD11c cells (including dendritic cells (DCs) and macrophages) are essential to mediate lipid presentation within the gut ultimately controlling intestinal NKT cell homeostasis and activation.

Tuning of in vivo cognate B-T cell interactions by Intersectin 2 is required for effective anti-viral B cell immunity.

Wiskott-Aldrich syndrome (WAS) is an immune pathology associated with mutations in WAS protein (WASp) or in WASp interacting protein (WIP). Together with the small GTPase Cdc42 and other effectors, these proteins participate in the remodelling of the actin network downstream of BCR engagement. Here we show that mice lacking the adaptor protein ITSN2, a G-nucleotide exchange factor (GEF) for Cdc42 that also interacts with WASp and WIP, exhibited increased mortality during primary infection, incomplete protection after Flu vaccination, reduced germinal centre formation and impaired antibody responses to vaccination.

Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells.

B cells constitute an essential line of defense from pathogenic infections through the generation of class-switched antibody-secreting cells (ASCs) in germinal centers. Although this process is known to be regulated by follicular helper T (TfH) cells, the mechanism by which B cells initially seed germinal center reactions remains elusive. We found that NKT cells, a population of innate-like T lymphocytes, are critical for the induction of B cell immunity upon viral infection.

Determination of some heavy metals in selected cosmetic products sold in kano metropolis, Nigeria.

The study was aimed at assessing the levels of some toxic metals in different cosmetic products sold at different shopping malls and markets in Kano Metropolis. The cosmetic items included ten face powder, ten skin lightening creams and ten lipsticks of various prices. The cosmetics were digested and analyzed for heavy metals (manganese, nickel, copper, cadmium, chromium and lead) using atomic absorption spectrophotometer.

A switch from canonical to noncanonical autophagy shapes B cell responses.

Autophagy is important in a variety of cellular and pathophysiological situations; however, its role in immune responses remains elusive. Here, we show that among B cells, germinal center (GC) cells exhibited the highest rate of autophagy during viral infection. In contrast to mechanistic target of rapamycin complex 1-dependent canonical autophagy, GC B cell autophagy occurred predominantly through a noncanonical pathway.

Host response. Inflammation-induced disruption of SCS macrophages impairs B cell responses to secondary infection.

The layer of macrophages at the subcapsular sinus (SCS) captures pathogens entering the lymph node, preventing their global dissemination and triggering an immune response. However, how infection affects SCS macrophages remains largely unexplored. Here we show that infection and inflammation disrupt the organization of SCS macrophages in a manner that involves the migration of mature dendritic cells to the lymph node.

Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity.

The small Rho GTPase Cdc42, known to interact with Wiskott-Aldrich syndrome (WAS) protein, is an important regulator of actin remodeling. Here, we show that genetic ablation of Cdc42 exclusively in the B cell lineage is sufficient to render mice unable to mount antibody responses. Indeed Cdc42-deficient mice are incapable of forming germinal centers or generating plasma B cells upon either viral infection or immunization.

Nck-mediated recruitment of BCAP to the BCR regulates the PI(3)K-Akt pathway in B cells.

The adaptor Nck links receptor signaling to cytoskeleton regulation. Here we found that Nck also controlled the phosphatidylinositol-3-OH kinase (PI(3)K)-kinase Akt pathway by recruiting the adaptor BCAP after activation of B cells. Nck bound directly to the B cell antigen receptor (BCR) via the non-immunoreceptor tyrosine-based activation motif (ITAM) phosphorylated tyrosine residue at position 204 in the tail of the immunoglobulin-α component.

Antiadipogenic effect of carnosic acid, a natural compound present in Rosmarinus officinalis, is exerted through the C/EBPs and PPARγ pathways at the onset of the differentiation program.

Background: Obesity is a serious health problem all over the world, and inhibition of adipogenesis constitutes one of the therapeutic strategies for its treatment. Carnosic acid (CA), the main bioactive compound of Rosmarinus officinalis extract, inhibits 3T3-L1 preadipocytes differentiation. However, very little is known about the molecular mechanism responsible for its antiadipogenic effect.

Pulse oximetry in the diagnosis of acute heart failure.

Introduction And Objectives: Oxygen saturation by pulse oximetry is commonly used for monitoring critical patients, but its utility as a diagnostic marker of acute heart failure has not been assessed. This study analyzed the diagnostic role of oxygen saturation by pulse oximetry in a series of patients with acute myocardial infarction.

Methods: In a prospective observational cohort study of 220 consecutive patients with acute myocardial infarction, data collection included baseline oxygen saturation by pulse oximetry (without oxygen), physiologic measurements, Killip class and data from portable chest radiography, recorded at the same hour on each of the first three days after admission.

[Infection and coronary atherosclerosis: the role Chlamydia pneumonia].

The role of inflammatory reactions in the pathogenesis of atherosclerosis is widely accepted. Recently, an increasing body of evidence has linked infections to atherosclerosis. It is hypothesized that infections could interact with other risk factors of vascular disease, enhancing the endothelial damage and the production of atherosclerotic plaques.