Psychological stress impairs IL22-driven protective gut mucosal immunity against colonising pathobionts.

Crohn's disease is an inflammatory disease of the gastrointestinal tract characterized by an aberrant response to microbial and environmental triggers. This includes an altered microbiome dominated by Enterobacteriaceae and in particular adherent-invasive E. coli (AIEC).

Low dietary fiber promotes enteric expansion of a Crohn's disease-associated pathobiont independent of obesity.

Obesity is associated with metabolic, immunological, and infectious disease comorbidities, including an increased risk of enteric infection and inflammatory bowel disease such as Crohn's disease (CD). Expansion of intestinal pathobionts such as adherent-invasive (AIEC) is a common dysbiotic feature of CD, which is amplified by prior use of oral antibiotics. Although high-fat, high-sugar diets are associated with dysbiotic expansion of , it is unknown if the content of fat or another dietary component in obesogenic diets is sufficient to promote AIEC expansion.

The Unique Lifestyle of Crohn's Disease-Associated Adherent-Invasive Escherichia coli.

Escherichia coli is one of the most genetically and phenotypically diverse species of bacteria. This remarkable diversity produces a plethora of clinical outcomes following infection and has informed much of what we currently know about host-pathogen interactions for a wide range of bacteria-host relationships. In studying the role of microbes in disease, adherent-invasive E.

Therapeutic control of leishmaniasis by inhibitors of the mammalian target of rapamycin.

Leishmaniasis is a serious global health problem affecting many people worldwide. While patients with leishmaniasis can be treated with several agents, drug toxicicty and the emergence of resistant strains render available treatments ineffective in the long run. Inhibitors of the mammalian target of rapamycin (mTOR) have been demonstrated to exert anti-pathogen properties.

Mucosa-associated invariant T cells in malignancies: a faithful friend or formidable foe?

Mucosa-associated invariant T (MAIT) cells are a subset of innate-like T lymphocytes known for their ability to respond to MHC-related protein 1 (MR1)-restricted stimuli and select cytokine signals. They are abundant in humans and especially enriched in mucosal layers, common sites of neoplastic transformation. MAIT cells have been found within primary and metastatic tumors.

PD-1 Blockade Promotes Epitope Spreading in Anticancer CD8 T Cell Responses by Preventing Fratricidal Death of Subdominant Clones To Relieve Immunodomination.

The interactions between programmed death-1 (PD-1) and its ligands hamper tumor-specific CD8 T cell (T) responses, and PD-1-based "checkpoint inhibitors" have shown promise in certain cancers, thus revitalizing interest in immunotherapy. PD-1-targeted therapies reverse T exhaustion/anergy. However, whether they alter the epitope breadth of T responses remains unclear.

Mucosa-associated invariant T cells infiltrate hepatic metastases in patients with colorectal carcinoma but are rendered dysfunctional within and adjacent to tumor microenvironment.

Mucosa-associated invariant T (MAIT) cells are innate-like T lymphocytes that are unusually abundant in the human liver, a common site of colorectal carcinoma (CRC) metastasis. However, whether they contribute to immune surveillance against colorectal liver metastasis (CRLM) is essentially unexplored. In addition, whether MAIT cell functions can be impacted by chemotherapy is unclear.

MAIT cells launch a rapid, robust and distinct hyperinflammatory response to bacterial superantigens and quickly acquire an anergic phenotype that impedes their cognate antimicrobial function: Defining a novel mechanism of superantigen-induced immunopathology and immunosuppression.

Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave.

The Future Liver Remnant in Patients Undergoing the Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy (ALPPS) Maintains the Immunological Components of a Healthy Organ.

Background And Aims: A short-interval, two-stage approach termed associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) increases the number of patients with extensive malignant disease of the liver and a small future liver remnant (FLR) that can undergo liver resection. While this approach results in accelerated liver hypertrophy of the FLR, it remains unknown whether this phenomenon is restricted to liver parenchymal cells. In the current study, we evaluated whether ALPPS alters the immunological composition of the deportalized lobe (DL) and the FLR.

Correction: Estradiol Enhances CD4+ T-Cell Anti-Viral Immunity by Priming Vaginal DCs to Induce Th17 Responses via an IL-1-Dependent Pathway.

[This corrects the article DOI: 10.1371/journal.ppat.

Estradiol Enhances CD4+ T-Cell Anti-Viral Immunity by Priming Vaginal DCs to Induce Th17 Responses via an IL-1-Dependent Pathway.

Clinical and experimental studies have shown that estradiol (E2) confers protection against HIV and other sexually transmitted infections. Here, we investigated the underlying mechanism. Better protection in E2-treated mice, immunized against genital HSV-2, coincided with earlier recruitment and higher proportions of Th1 and Th17 effector cells in the vagina post-challenge, compared to placebo-treated controls.

CD1d- and MR1-Restricted T Cells in Sepsis.

Dysregulated immune responses to infection, such as those encountered in sepsis, can be catastrophic. Sepsis is typically triggered by an overwhelming systemic response to an infectious agent(s) and is associated with high morbidity and mortality even under optimal critical care. Recent studies have implicated unconventional, innate-like T lymphocytes, including CD1d- and MR1-restricted T cells as effectors and/or regulators of inflammatory responses during sepsis.

Restoration of innate immune activation accelerates Th1-cell priming and protection following pulmonary mycobacterial infection.

The immune mechanisms underlying delayed induction of Th1-type immunity in the lungs following pulmonary mycobacterial infection remain poorly understood. We have herein investigated the underlying immune mechanisms for such delayed responses and whether a selected innate immune-modulating strategy can accelerate Th1-type responses. We have found that, in the early stage of pulmonary infection with attenuated Mycobacterium tuberculosis (M.

Continuous and discontinuous cigarette smoke exposure differentially affects protective Th1 immunity against pulmonary tuberculosis.

Pulmonary tuberculosis (TB), caused by Mycobacterium tuberculosis, is the leading cause of death due to a bacterial pathogen. Emerging epidemiologic evidence suggests that the leading risk factor associated with TB mortality is cigarette smoke exposure. Despite this, it remains poorly understood what is the effect of cigarette smoke exposure on anti-TB immunity and whether its potential detrimental effect can be reversed by cigarette smoking cessation.

Within the Enemy's Camp: contribution of the granuloma to the dissemination, persistence and transmission of Mycobacterium tuberculosis.

Pulmonary tuberculosis, caused by Mycobacterium tuberculosis (M.tb) represents a leading global health concern, with 8.7 million newly emerging cases, and 1.

Understanding delayed T-cell priming, lung recruitment, and airway luminal T-cell responses in host defense against pulmonary tuberculosis.

Mycobacterium tuberculosis (M.tb), the causative bacterium of pulmonary tuberculosis (TB), is a serious global health concern. Central to M.

Control of pathogenic CD4 T cells and lethal immunopathology by signaling immunoadaptor DAP12 during influenza infection.

Immunopathology is a major cause of influenza-associated morbidity and mortality worldwide. However, the role and regulatory mechanisms of CD4 T cells in severe lung immunopathology following acute influenza infection are poorly understood. In this paper, we report that the emergence of immunopathogenic CD4 T cells is under the control of a transmembrane immunoadaptor DAP12 pathway during influenza infection.

Pulmonary mycobacterial granuloma increased IL-10 production contributes to establishing a symbiotic host-microbe microenvironment.

The granuloma, a hallmark of host defense against pulmonary mycobacterial infection, has long been believed to be an active type 1 immune environment. However, the mechanisms regarding why granuloma fails to eliminate mycobacteria even in immune-competent hosts, have remained largely unclear. By using a model of pulmonary Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection, we have addressed this issue by comparing the immune responses within the airway luminal and granuloma compartments.

Pulmonary mucosal dendritic cells in T-cell activation: implications for TB therapy.

Mycobacterium tuberculosis, the causative agent of pulmonary TB, causes chronic intracellular infection of lung-resident antigen-presenting cells, including macrophages and dendritic cells (DCs). Life-long bacterial control requires robust T-cell immune responses. Lung DCs are critical for initiating and co-ordinating adaptive immune responses against TB.

Respiratory mucosal immunization with adenovirus gene transfer vector induces helper CD4 T cell-independent protective immunity.

Background: Virus-vectored vaccine is a powerful activator of CD8 T cell-mediated immunity and is especially amenable to respiratory mucosal immunization, offering hopes for use in humans with diminished helper CD4 T cell function. However, whether virus-mediated mucosal immunization can produce immune protective CD8 T cells without the CD4 T cell help remains to be investigated.

Methods: We used a replication-deficient adenovirus vector expressing an Mycobacterium tuberculosis antigen Ag85A for intranasal vaccination and evaluated its effect on CD8 T cell activation and protection in mice depleted of CD4 T cells.

Influenza infection leads to increased susceptibility to subsequent bacterial superinfection by impairing NK cell responses in the lung.

Influenza viral infection is well-known to predispose to subsequent bacterial superinfection in the lung but the mechanisms have remained poorly defined. We have established a murine model of heterologous infections by an H1N1 influenza virus and Staphylococcus aureus. We found that indeed prior influenza infection markedly increased the susceptibility of mice to secondary S.

Murine airway luminal antituberculosis memory CD8 T cells by mucosal immunization are maintained via antigen-driven in situ proliferation, independent of peripheral T cell recruitment.

Rationale: The airway luminal memory CD8 T cells induced by respiratory mucosal immunization in a murine model have been found to be critical to antituberculosis immunity. However, the mechanisms of their maintenance on airway mucosal surface still remain poorly understood.

Objectives: Using a model of adenovirus-based intranasal immunization we investigated the immune property and the mechanisms of maintenance of airway luminal CD8 T cells.

Mucosally delivered dendritic cells activate T cells independently of IL-12 and endogenous APCs.

In vitro manipulated dendritic cells (DC) have increasingly been used as a promising vaccine formulation against cancer and infectious disease. However, improved understanding of the immune mechanisms is needed for the development of safe and efficacious mucosal DC immunization. We have developed a murine model of respiratory mucosal immunization by using a genetically manipulated DC vaccine.