31 research outputs found
A-Kinase Anchoring in Dendritic Cells Is Required for Antigen Presentation
BACKGROUND: Dendritic cells (DC) are the most potent antigen presenting cells (APC) of the immune system. Prostaglandin E(2), cyclic AMP, and protein kinase A (PKA) have all been shown to regulate DC maturation and activity. In other cells, the ability of these molecules to convey their signals has been shown to be dependent on A-kinase anchoring proteins (AKAPs). Here we present evidence for the existence and functional importance of AKAPs in human DC. METHODOLOGY/PRINCIPAL FINDINGS: Using immunofluorescence and/or western analyses we identify AKAP79, AKAP149, AKAP95, AKAP LBC and Ezrin. We also demonstrate by western analysis that expression of AKAP79, AKAP149 and RII are upregulated with DC differentiation and maturation. We establish the functional importance of PKA anchoring in multiple aspects of DC biology using the anchoring inhibitor peptides Ht31 and AKAP-IS. Incubation of protein or peptide antigen loaded DC with Ht31 or AKAP-IS results in a 30-50% decrease in antigen presentation as measured by IFN-gamma production from antigen specific CD4(+) T cells. Incubation of LPS treated DC with Ht31 results in 80% inhibition of TNF-alpha and IL-10 production. Ht31 slightly decreases the expression of CD18 and CD11a and CD11b, slightly increases the basal expression of CD83, dramatically decreases the LPS stimulated expression of CD40, CD80 and CD83, and significantly increases the expression of the chemokine receptor CCR7. CONCLUSIONS: These experiments represent the first evidence for the functional importance of PKA anchoring in multiple aspects of DC biology
Synergistic Interactions between the NS3hel and E Proteins Contribute to the Virulence of Dengue Virus Type 1
Dengue virus constitutes a significant public health problem in tropical regions of the world. Despite the high morbidity and mortality of this infection, no effective antiviral drugs or vaccines are available for the treatment or prevention of dengue infections. The profile of clinical signs associated with dengue infection has changed in recent years with an increase in the number of episodes displaying unusual signs. We use reverse genetics technology to engineer DENV-1 viruses with subsets of mutations previously identified in highly neurovirulent strains to provide insights into the molecular mechanisms underlying dengue neuropathogenesis. We found that single mutations affecting the E and NS3hel proteins, introduced in a different genetic context, had a synergistic effect increasing DENV replication capacity in human and mosquito derived cells in vitro. We also demonstrated correlations between the presence of these mutations and viral replication efficiency, viral loads, the induction of innate immune response genes and pathogenesis in a mouse model. These results should improve our understanding of the DENV-host cell interaction and contribute to the development of effective antiviral strategies
What Is Direct Allorecognition?
Direct allorecognition is the process by which
donor-derived major histocompatibility complex (MHC)-peptide
complexes, typically presented by donor-derived ‘passenger’
dendritic cells, are recognised directly by recipient T cells.
In this review, we discuss the two principle theories which
have been proposed to explain why individuals possess a
high-precursor frequency of T cells with direct allospecificity
and how self-restricted T cells recognise allogeneic MHCpeptide
complexes. These theories, both of which are supported
by functional and structural data, suggest that T cells
recognising allogeneic MHC-peptide complexes focus either
on the allopeptides bound to the allo-MHC molecules or the
allo-MHC molecules themselves. We discuss how direct
alloimmune responses may be sustained long term, the consequences
of this for graft outcome and highlight novel strategies
which are currently being investigated as a potential
means of reducing rejection mediated through this pathway
Prediction of intracranial computed tomography findings in patients with minor head injury by using logistic regression
Calcificação nos núcleos da base na tomografia computadorizada: correlação clÃnica em 25 pacientes consecutivos Basal ganglia calcification on computed tomography: clinical characteristics in 25 patients
Analisamos os aspectos clÃnicos de 25 pacientes consecutivos que apresentaram calcificação nos núcleos da base na tomografia computadorizada (TC) de crânio. Esta ocorreu em 0,68% de todos os exames realizados no perÃodo. Vinte e três pacientes apresentavam condições clÃnicas diversas, a saber: cefaléia em 7 casos, acidente vascular cerebral em 5, sÃndrome extrapiramidal em 2, processo expansivo cerebral em 2, epilepsia, retardo do desenvolvimento neuropsicomotor, demência e trauma de crânio em um caso cada ou outras condições neurológicas em 3. Não havia sintomas neurológicos em 2 casos. Em 15 pacientes (60,0%) havia, além da calcificação dos núcleos da base, outras alterações na TC. Correlação clÃnica foi observada apenas com as outras alterações da TC e não com a calcificação dos núcleos da base, corroborando a hipótese de que esta possa ser um achado incidental.<br>Twenty-five patients presenting basal ganglia calcification were assessed. This finding comprised 0.68% of all skull CT scan carried out during the period. Two patients were neurologically asymptomatic and 23 presented a variety neurological disorders - headache (7 patients), stroke (5 patients), extrapyramidal syndromes (2 patients), tumor (2 patients), epilepsy (1 patient), mental retardation (1 patient), dementia (1 patient), cranial trauma (1 patient), other neurological conditions (3 patients) - or were asymptomatic from the neurological point of view (2 patients). Findings in the CT scan other than the basal ganglia calcification were observed in 15 (60%) patients. There was a clinical-CT scan correlation in these cases but not in those in which the basal ganglia calcification was an isolated finding. This study highlights the fact that basal ganglia calcification is often a nonspecific finding on CT scan and that it may not be possible to establish a clinical-pathological correlation between them
Evidence for the co-circulation of dengue virus type 3 genotypes III and V in the Northern region of Brazil during the 2002-2004 epidemics
The reintroduction of dengue virus type 3 (DENV-3) in Brazil in 2000 and its subsequent spread throughout the country was associated with genotype III viruses, the only DENV-3 genotype isolated in Brazil prior to 2002. We report here the co-circulation of two different DENV-3 genotypes in patients living in the Northern region of Brazil during the 2002-2004 epidemics. Complete genomic sequences of viral RNA were determined from these epidemics, and viruses belonging to genotypes V (Southeast Asia/South Pacific) and III were identified. This recent co-circulation of different DENV-3 genotypes in South America may have implications for pathological and epidemiological dynamics