Analysis of early childhood intestinal microbial dynamics in a continuous-flow bioreactor.

Background: The human gut microbiota is inoculated at birth and undergoes a process of assembly and diversification during the first few years of life. Studies in mice and humans have revealed associations between the early-life gut microbiome and future susceptibility to immune and metabolic diseases. To resolve microbe and host contributing factors to early-life development and to disease states requires experimental platforms that support reproducible, longitudinal, and high-content analyses.

Gut Microbiome Alterations Accompany Metabolic Normalization Following Bariatric Surgery in ROHHAD Syndrome.

Rapid onset obesity with hypoventilation, hypothalamic, and autonomic dysregulation (ROHHAD) syndrome in childhood is characterized by abrupt onset weight gain and dysautonomia with variable neuroendocrine involvement. In the absence of definitive disease-modifying therapies, the primary management strategy remains symptom control. This case report describes the first successful correction of obesity, dysautonomia, and metabolic derangement in a patient with ROHHAD following Roux-en-Y gastric bypass.

Cytotoxic CD4 T cells driven by T-cell intrinsic IL-18R/MyD88 signaling predominantly infiltrate -infected hearts.

Increasing attention has been directed to cytotoxic CD4 T cells (CD4CTLs) in different pathologies, both in humans and mice. The impact of CD4CTLs in immunity and the mechanisms controlling their generation, however, remain poorly understood. Here, we show that CD4CTLs abundantly differentiate during mouse infection with the intracellular parasite .

Phenotypic and functional changes in gamma delta T lymphocytes from HTLV-1 carriers.

Human T-cell lymphotropic virus type-1 (HTLV-1) is the etiologic agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which is a chronic inflammatory disease that leads to gradual loss of motor movement as a result of the death of spinal cord cells through immune mediated mechanisms. The risk to develop HAM/TSP disease positively correlates with the magnitude of HTLV-1 proviral load. Gamma-delta T lymphocytes have been recognized as important players in a variety of infectious diseases.

TLR9 Signaling Suppresses the Canonical Plasma Cell Differentiation Program in Follicular B Cells.

The relative potency and quality of mouse B cell response to Toll-like receptors (TLRs) signaling varies significantly depending on the B cell subset and on the TLR member being engaged. Although it has been shown that marginal zone cells respond faster than follicular (FO) splenic B cells to TLR4 stimulus, FO B cells retain full capacity to proliferate and generate plasmablasts and plasma cells (PBs/PCs) with 2-3 days delayed kinetics. It is not clear whether this scenario could be extended to other members of the TLR family.

Microbial symbionts regulate the primary Ig repertoire.

The ability of immunoglobulin (Ig) to recognize pathogens is critical for optimal immune fitness. Early events that shape preimmune Ig repertoires, expressed on IgM IgD B cells as B cell receptors (BCRs), are poorly defined. Here, we studied germ-free mice and conventionalized littermates to explore the hypothesis that symbiotic microbes help shape the preimmune Ig repertoire.

Circulating Plasma MicroRNA-208a as Potential Biomarker of Chronic Indeterminate Phase of Chagas Disease.

Chagas cardiomyopathy is the most severe clinical manifestation of chronic Chagas disease. The disease affects most of the Latin American countries, being considered one of the leading causes of morbidity and death in the continent. The pathogenesis of Chagas cardiomyopathy is very complex, with mechanisms involving parasite-dependent cytopathy, immune-mediated myocardial damage and neurogenic disturbances.

Stochasticity enables BCR-independent germinal center initiation and antibody affinity maturation.

Two immunoglobulin (Ig) diversification mechanisms collaborate to provide protective humoral immunity. Combinatorial assembly of and region exons from gene segments generates preimmune Ig repertoires, expressed as B cell receptors (BCRs). Secondary diversification occurs when regions undergo somatic hypermutation (SHM) and affinity-based selection toward antigen in activated germinal center (GC) B cells.

IgH isotype-specific B cell receptor expression influences B cell fate.

Ig heavy chain (IgH) isotypes (e.g., IgM, IgG, and IgE) are generated as secreted/soluble antibodies (sIg) or as membrane-bound (mIg) B cell receptors (BCRs) through alternative RNA splicing.

Crucial role for T cell-intrinsic IL-18R-MyD88 signaling in cognate immune response to intracellular parasite infection.

MyD88 is the main adaptor molecule for TLR and IL-1R family members. Here, we demonstrated that T-cell intrinsic MyD88 signaling is required for proliferation, protection from apoptosis and expression of activation/memory genes during infection with the intracellular parasite , as evidenced by transcriptome and cytometry analyses in mixed bone-marrow (BM) chimeras. The lack of direct IL-18R signaling in T cells, but not of IL-1R, phenocopied the absence of the MyD88 pathway, indicating that IL-18R is a critical MyD88-upstream pathway involved in the establishment of the Th1 response against an infection, a presently controvert subject.

Repression of Salmonella Host Cell Invasion by Aromatic Small Molecules from the Human Fecal Metabolome.

The human microbiome is a collection of microorganisms that inhabit every surface of the body that is exposed to the environment, generally coexisting peacefully with their host. These microbes have important functions, such as producing vitamins, aiding in maturation of the immune system, and protecting against pathogens. We have previously shown that a small-molecule extract from the human fecal microbiome has a strong repressive effect on serovar Typhimurium host cell invasion by modulating the expression of genes involved in this process.

Antarctic strict anaerobic microbiota from Deschampsia antarctica vascular plants rhizosphere reveals high ecology and biotechnology relevance.

The Antarctic soil microbial community has a crucial role in the growth and stabilization of higher organisms, such as vascular plants. Analysis of the soil microbiota composition in that extreme environmental condition is crucial to understand the ecological importance and biotechnological potential. We evaluated the efficiency of isolation and abundance of strict anaerobes in the vascular plant Deschampsia antarctica rhizosphere collected in the Antarctic's Admiralty Bay and associated biodiversity to metabolic perspective and enzymatic activity.

Enlarged colitogenic T cell population paradoxically supports colitis prevention through the B-lymphocyte-dependent peripheral generation of CD4(+)Foxp3(+) Treg cells.

Intestinal inflammation can be induced by the reconstitution of T/B cell-deficient mice with low numbers of CD4(+) T lymphocytes depleted of CD25(+)Foxp3(+) regulatory T cells (Treg). Using RAG-knockout mice as recipients of either splenocytes exclusively depleted of CD25(+) cells or FACS-purified CD4(+)CD25(-)Foxp3(-) T cells, we found that the augmentation of potentially colitogenic naïve T cell numbers in the inoculum was unexpectedly beneficial for the suppression of colon disease and maintenance of immune homeostasis. Protection against T cell-mediated colitis correlated with a significant increment in the frequency of peripherally-induced CD4(+)CD25(+)Foxp3(+) T (pTreg) cells, especially in the mesenteric lymph nodes, an effect that required the presence of B cells and CD4(+)CD25(-)Foxp3(+) cells in physiological proportions.

Primary immunoglobulin repertoire development: time and space matter.

The primary immunoglobulin repertoire develops via opposing forces of expanding diversification balanced by contracting selection mechanisms. The resulting shape is essential for host health and immune fitness. While the molecular mechanisms of Ig diversification have largely been defined, selection forces shaping emerging Ig repertoires are poorly understood.

IL-4 regulates Bim expression and promotes B cell maturation in synergy with BAFF conferring resistance to cell death at negative selection checkpoints.

IL-4 plays an essential role in the activation of mature B cells, but less is known about the role of IL-4 in B cell maturation and tolerance checkpoints. In this study, we analyzed the effect of IL-4 on in vitro B cell maturation, from immature to transitional stages, and its influence on BCR-mediated negative selection. Starting either from purified CD19(+)IgM(-) B cell precursors, or sorted bone marrow immature (B220(low)IgM(low)CD23(-)) and transitional (B220(int)IgM(high)CD23(-)) B cells from C57BL/6 mice, we compared the maturation effects of IL-4 and BAFF.

Inhibitors of DNA binding proteins restrict T cell potential by repressing Notch1 expression in Flt3-negative common lymphoid progenitors.

Lineage commitment is regulated during hematopoiesis, with stepwise loss of differentiation potential ultimately resulting in lineage commitment. In this study we describe a novel population of B/NK bipotent precursors among common lymphoid progenitors in the fetal liver and the bone marrow. The absence of T cell precursor potential, both in vivo and in vitro, is due to low Notch1 expression and secondary to inhibition of E2A activity by members of the inhibitor of DNA binding (Id) protein family.

TLR4 promotes B cell maturation: independence and cooperation with B lymphocyte-activating factor.

We have previously shown that TLR4 triggering promotes the generation of CD23(+)CD93(+) transitional T2-like cells in vitro from mouse B cell precursors, suggesting a possible role for this receptor in B cell maturation. In this study, we perform an extensive study of cell surface markers and functional properties of B cells matured in vitro with LPS, comparatively with the well-known B cell maturation factor B lymphocyte-activating factor (BAFF). LPS increased generation of CD23(+) transitional B cells in a TLR4-dependent way, upregulating IgD and CD21 and downregulating CD93, without inducing cell proliferation, in a manner essentially equivalent to BAFF.

Bradykinin B2 Receptors of dendritic cells, acting as sensors of kinins proteolytically released by Trypanosoma cruzi, are critical for the development of protective type-1 responses.

Although the concept that dendritic cells (DCs) recognize pathogens through the engagement of Toll-like receptors is widely accepted, we recently suggested that immature DCs might sense kinin-releasing strains of Trypanosoma cruzi through the triggering of G-protein-coupled bradykinin B2 receptors (B2R). Here we report that C57BL/6.B2R-/- mice infected intraperitoneally with T.