The glucose transporter 2 regulates CD8 T cell function via environment sensing.

T cell activation is associated with a profound and rapid metabolic response to meet increased energy demands for cell division, differentiation and development of effector function. Glucose uptake and engagement of the glycolytic pathway are major checkpoints for this event. Here we show that the low-affinity, concentration-dependent glucose transporter 2 (Glut2) regulates the development of CD8 T cell effector responses in mice by promoting glucose uptake, glycolysis and glucose storage.

Loss of mTORC2-induced metabolic reprogramming in monocytes uncouples migration and maturation from production of proinflammatory mediators.

Monocyte migration to the sites of inflammation and maturation into macrophages are key steps for their immune effector function. Here, we show that mechanistic target of rapamycin complex 2 (mTORC2)-dependent Akt activation is instrumental for metabolic reprogramming at the early stages of macrophage-mediated immunity. Despite an increased production of proinflammatory mediators, monocytes lacking expression of the mTORC2 component Rictor fail to efficiently migrate to inflammatory sites and fully mature into macrophages, resulting in reduced inflammatory responses in vivo.

Lung Marginated and Splenic Murine Resident Neutrophils Constitute Pioneers in Tissue-Defense During Systemic Challenge.

The rapid response of neutrophils throughout the body to a systemic challenge is a critical first step in resolution of bacterial infection such as (). Here we delineated the dynamics of this response, revealing novel insights into the molecular mechanisms using lung and spleen intravital microscopy and 3D culture of living precision cut splenic slices in combination with fluorescent labelling of endogenous leukocytes. Within seconds after challenge, intravascular marginated neutrophils and lung endothelial cells (ECs) work cooperatively to capture pathogens.

Metabolic regulation of T lymphocyte motility and migration.

In order to fulfill their effector and patrolling functions, lymphocytes traffic through the body and need to adapt to different tissue microenvironments. First, mature lymphocytes egress the bone marrow and the thymus into the vascular system. Circulating lymphocytes can exit the vasculature and penetrate into the tissues, either for patrolling in search for pathogens or to eliminate infection and activate the adaptive immune response.

Preservation of microvascular barrier function requires CD31 receptor-induced metabolic reprogramming.

Endothelial barrier (EB) breaching is a frequent event during inflammation, and it is followed by the rapid recovery of microvascular integrity. The molecular mechanisms of EB recovery are poorly understood. Triggering of MHC molecules by migrating T-cells is a minimal signal capable of inducing endothelial contraction and transient microvascular leakage.

Polymorphism, Nasopharyngeal Bacterial Colonization, and the Development of Childhood Asthma: A Prospective Birth-Cohort Study in Finnish Children.

We aimed to explore the role of TLR4 (rs4986790) polymorphism in the nasopharyngeal (NP) bacterial colonization and its consequent impact on the development of childhood asthma. A semi-quantitative culture of NP swabs was performed on 473 children at 2 months of age and on 213 children at 13 months of age. polymorphism was analyzed for 396 children.

Neutrophils restrain allergic airway inflammation by limiting ILC2 function and monocyte-dendritic cell antigen presentation.

Neutrophil mobilization, recruitment, and clearance must be tightly regulated as overexuberant neutrophilic inflammation is implicated in the pathology of chronic diseases, including asthma. Efforts to target neutrophils therapeutically have failed to consider their pleiotropic functions and the implications of disrupting fundamental regulatory pathways that govern their turnover during homeostasis and inflammation. Using the house dust mite (HDM) model of allergic airway disease, we demonstrate that neutrophil depletion unexpectedly resulted in exacerbated T helper 2 (T2) inflammation, epithelial remodeling, and airway resistance.

Pulmonary environmental cues drive group 2 innate lymphoid cell dynamics in mice and humans.

Group 2 innate lymphoid cells (ILC2s) are enriched in mucosal tissues (e.g., lung) and respond to epithelial cell-derived cytokines initiating type 2 inflammation.

Interleukin-10 gene polymorphism rs1800896 is associated with post-bronchiolitis asthma at 11-13 years of age.

Aim: Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is involved with bronchiolitis and asthma. We evaluated associations between four IL-10 polymorphisms, namely rs1800871, rs1800872, rs1800890 and rs1800896, and post-bronchiolitis asthma in young adolescents.

Methods: The cohort consisted of 125 children hospitalised for bronchiolitis at Tampere University Hospital, Finland, in 2000-2004, at less than six months of age.

Polymorphisms in the promoter region of IL10 gene are associated with virus etiology of infant bronchiolitis.

Background: Bronchiolitis is the most common infection leading to hospitalization in infancy. Interleukin-10 (IL-10) is an anti-inflammatory cytokine, and in our previous study, IL10 gene rs1800896 (- 1082A/G) polymorphism was associated with viral etiology of infant bronchiolitis. The objective of this study was to evaluate the associations between IL10 single nucleotide polymorphisms (SNPs) at rs1800890 (- 3575A/T), rs1800871 (- 819C/T) or rs1800872 (- 592C/A) either alone or combined with the SNP at rs1800896 (- 1082G/A), and the etiology and severity of infant bronchiolitis.

Haplotype of the Interleukin 17A gene is associated with osteitis after Bacillus Calmette-Guerin vaccination.

Bacillus Calmette-Guerin (BCG) osteitis was more common in Finland than elsewhere at the time when universal BCG vaccinations were given to Finnish newborns. There is evidence that IL-17 plays a role in the defense against tuberculosis. The aim of this study was to evaluate the associations of IL17A rs4711998, IL17A rs8193036 and IL17A rs2275913 single-nucleotide polymorphisms (SNPs) with the risk of BCG osteitis after newborn vaccination.

Interleukin 17A gene polymorphism rs2275913 is associated with osteitis after the Bacillus Calmette-Guérin vaccination.

Aim: Interleukin-17 (IL-17) appears to promote the host's defence against mycobacterial infections. This study evaluated the association between IL17A gene polymorphism and the risk of Bacillus Calmette-Guérin (BCG) osteitis after newborn vaccination and between IL17A gene polymorphism and IL-17A concentrations in serum.

Methods: IL17A rs2275913 gene polymorphisms and serum IL-17A concentrations were studied in 132 adults aged 21-49 years from across Finland, who had BCG osteitis in infancy after a newborn BCG vaccination.

Toll-like receptor 1 and 10 gene polymorphisms are linked to postbronchiolitis asthma in adolescence.

Aim: Toll-like receptors (TLR) are innate immunity molecules and our previous studies found that TLR1 gene polymorphism was associated with postbronchiolitis asthma at one to six years of age, as was TLR10 at five to seven years of age. This study examined any associations at 11-13 years of age.

Methods: This prospective follow-up study was part of an ongoing evaluation of children admitted to Tampere University Hospital, Finland, for bronchiolitis in 2001-2004 at less than six months of age.

Polymorphism in the gene encoding toll-like receptor 10 may be associated with asthma after bronchiolitis.

Toll-like receptors (TLRs) recognise microbes that contribute to the severity of bronchiolitis and the subsequent risk of asthma. We evaluated whether post-bronchiolitis asthma was associated with polymorphisms in the TLR3 rs3775291, TLR4 rs4986790, TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084, and TLR10 rs4129009 genes. The gene polymorphisms were studied at the age of 6.

Polymorphisms of Mannose-binding Lectin and Toll-like Receptors 2, 3, 4, 7 and 8 and the Risk of Respiratory Infections and Acute Otitis Media in Children.

Background: Mannose-binding lectin (MBL) and toll-like receptors (TLRs) are important components of the innate immune system. We assessed the susceptibility of children with genetic variants in these factors to respiratory infections, rhinovirus infections and acute otitis media.

Methods: In a prospective cohort study, blood samples from 381 Finnish children were analyzed for polymorphisms in MBL2 at codons 52, 54 and 57, TLR2 Arg753Gln, TLR3 Leu412Phe, TLR4 Asp299Gly, TLR7 Gln11Leu and TLR8 Leu651Leu.

Post-bronchiolitis wheezing is associated with toll-like receptor 9 rs187084 gene polymorphism.

Innate immunity receptors play a critical role in host defence, as well as in allergy and asthma. The aim of this exploratory study was to evaluate whether there are associations between TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084 or TLR10 rs4129009 polymorphisms and viral findings, clinical characteristics or subsequent wheezing in infants with bronchiolitis. In all, 135 full-term infants were hospitalized for bronchiolitis at age less than 6 months: 129 of them were followed-up until the age of 1.

Burden of Recurrent Respiratory Tract Infections in Children: A Prospective Cohort Study.

Background: The burden of recurrent respiratory infections is unclear. We identified young children with recurrent respiratory infections in order to characterize the clinical manifestations, risk factors and short-term consequences.

Methods: In this prospective cohort study, 1089 children were followed from birth to 2 years of age for respiratory infections by a daily symptom diary.

IL-10 gene polymorphism is associated with preschool atopy and early-life recurrent wheezing after bronchiolitis in infancy.

Background: Variations in the genes that regulate innate immunity responses may be associated with susceptibility to asthma or atopy after early-life bronchiolitis. The aim of this study was to evaluate the association between four different polymorphisms of the IL-10 gene at rs1800871, rs1800872, rs1800890, and rs1800896, either alone or in combination, and post-bronchiolitis asthma or allergies at 5-7 years of age.

Methods: Data on single nucleotide polymorphisms (SNP) of IL-10 rs1800896 (-1082G/A), rs1800871 (-819C/T), rs1800872 (-592C/A), and IL-10 rs1800890 (-3575T/A) were available for 135 children.

Gene Polymorphism of Toll-Like Receptors and Lung Function at Five to Seven Years of Age after Infant Bronchiolitis.

Aim: Toll-like receptors (TLR) play a crucial role in innate immunity, protecting the host from pathogens such as viruses. Genetic variations in TLRs have been associated with the severity of viral bronchiolitis in infancy and with the later occurrence of post-bronchiolitis asthma. The aim of the present study was to evaluate if there are any exploratory associations between TLR gene polymorphisms and lung function at 5 to 7 years of age in former bronchiolitis patients.

IL-10 Gene Polymorphisms Are Associated with Post-Bronchiolitis Lung Function Abnormalities at Six Years of Age.

Aim: Interleukin-10 (IL-10) has been associated with wheezing and asthma in children and the genetic variation of the IL-10 cytokine production may be linked to post-bronchiolitis lung function. We used impulse oscillometry (IOS) to evaluate the associations of IL10 polymorphisms with lung function at a median age of 6.3 years in children hospitalised for bronchiolitis before six months of age.

The Gene Polymorphism of IL-17 G-152A is Associated with Increased Colonization of Streptococcus pneumoniae in Young Finnish Children.

Background: Streptococcus pneumoniae is a common respiratory pathogen, and up to 50% of children acquire S. pneumoniae in their nasopharynx during the first 12 months of life. The cytokine interleukin-17A (IL-17A) plays an important role in host defense against extracellular bacterial pathogens.

Toll-like receptor 2 subfamily gene polymorphisms are associated with Bacillus Calmette-Guérin osteitis following newborn vaccination.

Aim: Toll-like receptor (TLR) 1, 2, 6 and 10, the TLR2 subfamily, are known to be associated with immunity against tuberculosis. We evaluated whether polymorphisms in genes encoding TLR1, TLR2 and TLR6 were associated with osteitis in infants who received the Bacillus Calmette-Guérin (BCG) vaccination soon after birth.

Methods: Blood samples from 132 adults aged 21-49 who had BCG osteitis in early childhood were analysed in a controlled study for TLR1 T1805G (rs5743618), TLR2 G2258A (rs5743708) and TLR6 C745T (rs5743810) gene single nucleotide polymorphisms.