Intranasal exposure to commensal bacterium Rothia mucilaginosa protects against influenza A virus infection.

The respiratory tract hosts a diverse microbial community whose composition varies with anatomical location and throughout life. Rothia mucilaginosa, a common commensal of the upper respiratory tract and oral cavity, has recently been recognized for its ability to inhibit bacteria-triggered pro-inflammatory responses. However, its role in modulating the immune response to viral infections such as influenza A virus (IAV) pneumonia, remains unknown.

Description of a Murine Model of Pneumocystis Pneumonia.

Pneumocystis pneumonia is a serious lung infection caused by an original ubiquitous fungus with opportunistic behavior, referred to as Pneumocystis jirovecii. P. jirovecii is the second most common fungal agent among invasive fungal infections after Candida spp.

Deconstructing iNKT cell development at single-cell resolution.

Invariant natural killer T (iNKT) cells are increasingly regarded as disease biomarkers and immunotherapeutic targets. However, a greater understanding of their biology is necessary to effectively target these cells in the clinic. The discovery of iNKT1/2/17 cell effector subsets was a milestone in our understanding of iNKT cell development and function.

Host succinate inhibits influenza virus infection through succinylation and nuclear retention of the viral nucleoprotein.

Influenza virus infection causes considerable morbidity and mortality, but current therapies have limited efficacy. We hypothesized that investigating the metabolic signaling during infection may help to design innovative antiviral approaches. Using bronchoalveolar lavages of infected mice, we here demonstrate that influenza virus induces a major reprogramming of lung metabolism.

Pneumonia: Pitfalls and Hindrances to Establishing a Reliable Animal Model.

pneumonia is a severe lung infection that occurs primarily in largely immunocompromised patients. Few treatment options exist, and the mortality rate remains substantial. To develop new strategies in the fields of diagnosis and treatment, it appears to be critical to improve the scientific knowledge about the biology of the agent and the course of the disease.

Recruitment and activation of type 3 innate lymphoid cells promote antitumor immune responses.

Tumors poorly infiltrated by T cells are more resistant to immunogenic chemotherapies and checkpoint inhibition than highly infiltrated tumors. Using murine models, we found that CCR6 type 3 innate lymphoid cells (ILC3s) can trigger an increase in the number of T cells infiltrating a tumor. Shortly after administration of cisplatin chemotherapy, production of the chemokine CCL20 and proinflammatory cytokine IL-1β at the tumor site led to the recruitment and activation of ILC3s.

Regulation and Functions of Protumoral Unconventional T Cells in Solid Tumors.

The vast majority of studies on T cell biology in tumor immunity have focused on peptide-reactive conventional T cells that are restricted to polymorphic major histocompatibility complex molecules. However, emerging evidence indicated that unconventional T cells, including γδ T cells, natural killer T (NKT) cells and mucosal-associated invariant T (MAIT) cells are also involved in tumor immunity. Unconventional T cells span the innate-adaptive continuum and possess the unique ability to rapidly react to nonpeptide antigens via their conserved T cell receptors (TCRs) and/or to activating cytokines to orchestrate many aspects of the immune response.

Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity.

Immune system dysfunction is paramount in coronavirus disease 2019 (COVID-19) severity and fatality rate. Mucosal-associated invariant T (MAIT) cells are innate-like T cells involved in mucosal immunity and protection against viral infections. Here, we studied the immune cell landscape, with emphasis on MAIT cells, in cohorts totaling 208 patients with various stages of disease.

Proteinase release from activated neutrophils in mechanically ventilated patients with non-COVID-19 and COVID-19 pneumonia.

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a new class of biopharmaceuticals in the therapeutic arsenal against cancer.

Background: Microorganisms that can be used for their lytic activity against tumor cells as well as inducing or reactivating antitumor immune responses are a relevant part of the available immunotherapy strategies. Viruses, bacteria and even protozoa have been largely explored with success as effective human antitumor agents. To date, only one oncolytic virus-T-VEC-has been approved by the US Food and Drug Administration for use in biological cancer therapy in clinical trials.

Phenotypical and functional alteration of unconventional T cells in severe COVID-19 patients.

COVID-19 includes lung infection ranging from mild pneumonia to life-threatening acute respiratory distress syndrome (ARDS). Dysregulated host immune response in the lung is a key feature in ARDS pathophysiology. However, cellular actors involved in COVID-19-driven ARDS are poorly understood.

Cigarette smoke induces overexpression of active human cathepsin S in lungs from current smokers with or without COPD.

Cigarette smoking has marked effects on lung tissue, including induction of oxidative stress, inflammatory cell recruitment, and a protease/antiprotease imbalance. These effects contribute to tissue remodeling and destruction resulting in loss of lung function in chronic obstructive pulmonary disease (COPD) patients. Cathepsin S (CatS) is a cysteine protease that is involved in the remodeling/degradation of connective tissue and basement membrane.

Lipoxygenase LoxA Contributes to Lung Infection by Altering the Host Immune Lipid Signaling.

is an opportunistic bacteria and a major cause of nosocomial pneumonia. has many virulence factors contributing to its ability to colonize the host. LoxA is a lipoxygenase enzyme secreted by that oxidizes polyunsaturated fatty acids.

Tissue kallikrein regulates alveolar macrophage apoptosis early in influenza virus infection.

Host cell proteases are involved in influenza pathogenesis. We examined the role of tissue kallikrein 1 (KLK1) by comparing wild-type (WT) and KLK1-deficient mice infected with influenza H3N2 virus. The levels of KLK1 in lung tissue and in bronchoalveolar lavage (BAL) fluid increased substantially during infection.

Lack of FcRn Impairs Natural Killer Cell Development and Functions in the Tumor Microenvironment.

The neonatal Fc receptor (FcRn) is responsible for the recycling and transcytosis of IgG and albumin. FcRn level was found altered in cancer tissues and implicated in tumor immunosurveillance and neoplastic cell growth. However, the consequences of FcRn down-regulation in the anti-tumor immune response are not fully elucidated.

Impact of the TAP-like transporter in antigen presentation and phagosome maturation.

Cross-presentation is thought to require transport of proteasome-generated peptides by the TAP transporters into MHC class I loading compartments for most antigens. However, a proteasome-dependent but TAP-independent pathway has also been described. Depletion of the pool of recycling cell surface MHC class I molecules available for loading with cross-presented peptides might partly or largely account for the critical role of TAP in cross-presentation of phagocytosed antigens.

Thymic Program Directing the Functional Development of γδT17 Cells.

γδT cells comprise a unique T cell sublineage endowed with a wide functional repertoire, which allow them to play important-sometimes opposite-roles in many immune responses associated with infection, cancer, and inflammatory processes. This is largely dependent on the existence of pre-programmed discrete functional subsets that differentiate within the thymus at specific temporal windows of life. Since they represent a major early source of interleukin-17A in many models of immune responses, the γδT17 cell population has recently gained considerable interest.

Exploration of the role of the virulence factor ElrA during Enterococcus faecalis cell infection.

Enterococcus faecalis, an organism generally not pathogenic for healthy humans, has the potential to cause disease in susceptible hosts. While it seems to be equipped to interact with and circumvent host immune defense, most of the molecular and cellular mechanisms underlying the enterococcal infectious process remain elusive. Here, we investigated the role of the Enterococcal Leucine Rich protein A (ElrA), an internalin-like protein of E.

Kallikrein-Related Peptidase 5 Contributes to H3N2 Influenza Virus Infection in Human Lungs.

Hemagglutinin (HA) of influenza virus must be activated by proteolysis before the virus can become infectious. Previous studies indicated that HA cleavage is driven by membrane-bound or extracellular serine proteases in the respiratory tract. However, there is still uncertainty as to which proteases are critical for activating HAs of seasonal influenza A viruses (IAVs) in humans.

FHL2 Regulates Natural Killer Cell Development and Activation during Infection.

Recent studies suggested that the transcription cofactor LIM-only protein FHL2 is a major transcriptional regulator of mouse natural killer (NK) cells. However, the expression and role of FHL2 in NK cell biology are unknown. Here, we confirm that FHL2 is expressed in both mouse and human NK cells.

Prolonged pharmacological inhibition of cathepsin C results in elimination of neutrophil serine proteases.

Cathepsin C (CatC) is a tetrameric cysteine dipeptidyl aminopeptidase that plays a key role in activation of pro-inflammatory serine protease zymogens by removal of a N-terminal pro-dipeptide sequence. Loss of function mutations in the CatC gene is associated with lack of immune cell serine protease activities and cause Papillon-Lefèvre syndrome (PLS). Also, only very low levels of elastase-like protease zymogens are detected by proteome analysis of neutrophils from PLS patients.