Diagnostic comparison of malaria infection in peripheral blood, placental blood and placental biopsies in Cameroonian parturient women

<p>Abstract</p> <p>Background</p> <p>In sub-Saharan Africa, <it>Plasmodium falciparum </it>malaria in pregnancy presents an enormous diagnostic challenge. The epidemiological and clinical relevance of the different types of malaria diagnosis as well as risk factors associated with malaria infection at delivery were investigated.</p> <p>Method</p> <p>In a cross-sectional survey, 306 women reporting for delivery in the Mutenegene maternity clinic, Fako division, South West province, Cameroon were screened for <it>P. falciparum </it>in peripheral blood, placental blood and placental tissue sections by microscopy. Information relating to the use of intermittent preventive treatment in pregnancy with sulphadoxine/pyrimethamine, history of fever attack, infant birth weights and maternal anaemia were recorded.</p> <p>Results</p> <p>Among these women, <it>P. falciparum </it>infection was detected in 5.6%, 25.5% and 60.5% of the cases in peripheral blood, placental blood and placental histological sections respectively. Placental histology was more sensitive (97.4%) than placental blood film (41.5%) and peripheral blood (8.0%) microscopy. In multivariate analysis, age (≤ 20 years old) (OR = 4.61, 95% CI = 1.47 – 14.70), history of fever attack (OR = 2.98, 95% CI = 1.58 – 5.73) were significant risk factors associated with microscopically detected parasitaemia. The use of ≥ 2 SP doses (OR = 0.18, 95% CI = 0.06 – 0.52) was associated with a significant reduction in the prevalence of microscopic parasitaemia at delivery. Age (>20 years) (OR = 0.34, 95% CI = 0.15 – 0.75) was the only significant risk factor associated with parasitaemia diagnosed by histology only in univariate analysis. Microscopic parasitaemia (OR = 2.74, 95% CI = 1.33–5.62) was a significant risk factor for maternal anaemia at delivery, but neither infection detected by histology only, nor past infection were associated with increased risk of anaemia.</p> <p>Conclusion</p> <p>Placenta histological examination was the most sensitive indicator of malaria infection at delivery. Microscopically detected parasitaemia was associated with increased risk of maternal anaemia at delivery, but not low-grade parasitaemia detected by placental histology only.</p

Peanut sensitization during the first five years of life is associated with elevated levels of peanut-specific IgG

Background: Allergen-specific IgE antibodies are implicated in allergic diseases while allergen-specific IgG antibodies have been proposed to prevent allergic reactions. The objective for this study was to study if the immune response (IgG and IgG4) to peanut differs in IgE sensitized and non-sensitized young children. Methods: A total of 239 children have been followed prospectively from birth to 5 years of age. Levels of IgG and IgG4 to peanut, Ara h 2 and Ara h 8 were analyzed at 2 and 5 years of age and related to IgE-sensitization and peanut consumption. Results:  Levels of peanut-specific IgG and IgG4 were significantly higher in peanut-sensitized children at 2 and 5 years of age when compared to non-sensitized children and children sensitized to other food/inhalant allergens. A strong correlation was seen between levels of peanut-specific IgG/IgG4-ratios and peanut-specific IgE at 5 years of age. Children avoiding peanuts, a subgroup of the peanut sensitized, had statistically significant higher levels of IgE to peanut and a tendency of higher IgG and IgG4 levels to peanut. In the avoidance-group significant correlations between IgE and IgG/IgG4 to peanut was found compared to children eating peanuts.  Conclusion: Peanut-specific IgG or IgG4 levels were elevated in peanut-sensitized children especially those avoiding peanuts. In our study, IgG and IgG4 do not seem to indicate tolerance or protection from sensitization

Allergic women have reduced sHLA-G plasma levels at delivery

Problem HLA-G antigen maintains a tolerogenic condition at the feto-maternal interface, counteracts inflammation in autoimmune diseases and soluble HLA-G (sHLA-G) levels decrease in allergic-asthmatics. Taking into consideration these findings we analyzed if sHLA-G and IL-10 could be influenced by pregnancy and labour in allergic and non-allergic women. Method of Study sHLA-G isoforms and interleukin 10 (IL-10) levels were determined in the plasma samples of 43 women (15 non-allergic, 28 allergic) during third trimester, at delivery and 2 years after pregnancy by immunoenzymatic assays. Results A significant increase in sHLA-G and IL-10 levels was documented at delivery in both allergic and non-allergic women. Allergic women showed lower sHLA-G concentrations. sHLA-G1 was evidenced as the predominant plasma isoform. Conclusions The data propose an impressive boost in sHLA-G and IL-10 concentrations at delivery, regardless of the allergic status. The sHLA-G1 isoform is the main responsible for the increased sHLA-G levels at delivery

Relationship between maternal and child cytokine responses to allergen and phytohaemagglutinin 2 years after delivery

Little is known at present about the relation between parental and child cytokine profiles. In this study we aimed to investigate the cytokine profile of 2-year-old children and their corresponding mothers, 2 years after delivery. Peripheral blood mononuclear cells (PBMC) were isolated from IgE-sensitized (n = 15) and non-sensitized (n = 58) 2-year-old children and their mothers. The responses to ovalbumin, cat and phytohaemagglutinin (PHA) were investigated using the enzyme-linked immunospot (ELISpot) technique. Interferon (IFN)-γ-, interleukin (IL)-4-, IL-10- and IL-12-producing cells were enumerated. At 2 years of age, IgE-sensitized children exhibited increased numbers of IL-4-producing cells in response to PHA and also showed an increase in IL-10- and IL-12-producing cells to allergen that was more pronounced in response to ovalbumin than to cat. A statistically significant increase in the numbers of IFN-γ-, IL-10- and IL-12-producing cells to the allergens, but not to PHA, was found in the mothers of IgE-sensitized children irrespective of their own atopic status. IgE levels and cytokine responses were correlated between the mothers and their children, indicating that cytokine responses to both allergen and PHA might be governed by genetic factors. We speculate that the increased cytokine response to allergen, as opposed to the allergic status of the mother, might be a better predictor and/or a risk factor for the child to develop IgE-sensitization in early life

Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses

Introduction Among sensitized infants, those with high, as compared with low levels, of salivary secretory IgA (SIgA) are less likely to develop allergic symptoms. Also, early colonization with certain gut microbiota, e.g. Lactobacilli and Bifidobacterium species, might be associated with less allergy development. Although animal and in vitro studies emphasize the role of the commensal gut microbiota in the development of the immune system, the influence of the gut microbiota on immune development in infants is unclear. Objective To assess whether early colonization with certain gut microbiota species associates with mucosal and systemic immune responses i.e. salivary SIgA and the spontaneous Toll-like receptor (TLR) 2 and TLR4 mRNA expression and lipopolysaccharide (LPS)-induced cytokine/chemokine responses in peripheral blood mononuclear cells (PBMCs). Methods Fecal samples were collected at 1 week, 1 month and 2 months after birth from 64 Swedish infants, followed prospectively up to 5 years of age. Bacterial DNA was analysed with real-time PCR using primers binding to Clostridium difficile, four species of bifidobacteria, two lactobacilli groups and Bacteroides fragilis. Saliva was collected at age 6 and 12 months and at 2 and 5 years and SIgA was measured with ELISA. The PBMCs, collected 12 months after birth, were analysed for TLR2 and TLR4 mRNA expression with real-time PCR. Further, the PBMCs were stimulated with LPS, and cytokine/chemokine responses were measured with Luminex. Results The number of Bifidobacterium species in the early fecal samples correlated significantly with the total levels of salivary SIgA at 6 months. Early colonization with Bifidobacterium species, lactobacilli groups or C. difficile did not influence TLR2 and TLR4 expression in PBMCs. However, PBMCs from infants colonized early with high amounts of Bacteroides fragilis expressed lower levels of TLR4 mRNA spontaneously. Furthermore, LPS-induced production of inflammatory cytokines and chemokines, e.g. IL-6 and CCL4 (MIP-1β), was inversely correlated to the relative amounts of Bacteroides fragilis in the early fecal samples. Conclusion Bifidobacterial diversity may enhance the maturation of the mucosal SIgA system and early intense colonization with Bacteroides fragilis might down-regulate LPS responsiveness in infancy

Inhibition of Type III Interferon Expression in Intestinal Epithelial Cells—A Strategy Used by Coxsackie B Virus to Evade the Host’s Innate Immune Response at the Primary Site of Infection?

Increasing evidence highlights the importance of the antiviral activities of the type III interferons (IFN&lambda;s; IL-28A, IL-28B, IL29, and IFN&lambda;4) in the intestine. However, many viruses have developed strategies to counteract these defense mechanisms by preventing the production of IFNs. Here we use infection models, a clinical virus isolate, and several molecular biology techniques to demonstrate that both type I and III IFNs induce an antiviral state and attenuate Coxsackievirus group B (CVB) replication in human intestinal epithelial cells (IECs). While treatment of IECs with a viral mimic (poly (I:C)) induced a robust expression of both type I and III IFNs, no such up-regulation was observed after CVB infection. The blunted IFN response was paralleled by a reduction in the abundance of proteins involved in the induction of interferon gene transcription, including TIR-domain-containing adapter-inducing interferon-&beta; (TRIF), mitochondrial antiviral-signaling protein (MAVS), and the global protein translation initiator eukaryotic translation initiation factor 4G (eIF4G). Taken together, this study highlights a potent anti-Coxsackieviral effect of both type I and III IFNs in cells located at the primary site of infection. Furthermore, we show for the first time that the production of type I and III IFNs in IECs is blocked by CVBs. These findings suggest that CVBs evade the host immune response in order to successfully infect the intestine

Shared and Distinct Phenotypes and Functions of Human CD161++ Vα7.2+ T Cell Subsets.

Human mucosal-associated invariant T (MAIT) cells are an important T cell subset that are enriched in tissues and possess potent effector functions. Typically such cells are marked by their expression of Vα7.2-Jα33/Jα20/Jα12 T cell receptors, and functionally they are major histocompatibility complex class I-related protein 1 (MR1)-restricted, responding to bacterially derived riboflavin synthesis intermediates. MAIT cells are contained within the CD161++ Vα7.2+ T cell population, the majority of which express the CD8 receptor (CD8+), while a smaller fraction expresses neither CD8 or CD4 coreceptor (double negative; DN) and a further minority are CD4+. Whether these cells have distinct homing patterns, phenotype and functions have not been examined in detail. We used a combination of phenotypic staining and functional assays to address the similarities and differences between these CD161++ Vα7.2+ T cell subsets. We find that most features are shared between CD8+ and DN CD161++ Vα7.2+ T cells, with a small but detectable role evident for CD8 binding in tuning functional responsiveness. By contrast, the CD4+ CD161++ Vα7.2+ T cell population, although showing MR1-dependent responsiveness to bacterial stimuli, display reduced T helper 1 effector functions, including cytolytic machinery, while retaining the capacity to secrete interleukin-4 (IL-4) and IL-13. This was consistent with underlying changes in transcription factor (TF) expression. Although we found that only a proportion of CD4+ CD161++ Vα7.2+ T cells stained for the MR1-tetramer, explaining some of the heterogeneity of CD4+ CD161++ Vα7.2+ T cells, these differences in TF expression were shared with CD4+ CD161++ MR1-tetramer+ cells. These data reveal the functional diversity of human CD161++ Vα7.2+ T cells and indicate potentially distinct roles for the different subsets in vivo

Shared and distinct phenotypes and functions of human CD161++ Vα7.2+ T cell subsets

Human mucosal-associated invariant T (MAIT) cells are an important T cell subset that are enriched in tissues and possess potent effector functions. Typically such cells are marked by their expression of Vα7.2-Jα33/Jα20/Jα12 T cell receptors, and functionally they are major histocompatibility complex class I-related protein 1 (MR1)-restricted, responding to bacterially derived riboflavin synthesis intermediates. MAIT cells are contained within the CD161++ Vα7.2+ T cell population, the majority of which express the CD8 receptor (CD8+), while a smaller fraction expresses neither CD8 or CD4 coreceptor (double negative; DN) and a further minority are CD4+. Whether these cells have distinct homing patterns, phenotype and functions have not been examined in detail. We used a combination of phenotypic staining and functional assays to address the similarities and differences between these CD161++ Vα7.2+ T cell subsets. We find that most features are shared between CD8+ and DN CD161++ Vα7.2+ T cells, with a small but detectable role evident for CD8 binding in tuning functional responsiveness. By contrast, the CD4+ CD161++ Vα7.2+ T cell population, although showing MR1-dependent responsiveness to bacterial stimuli, display reduced T helper 1 effector functions, including cytolytic machinery, while retaining the capacity to secrete interleukin-4 (IL-4) and IL-13. This was consistent with underlying changes in transcription factor (TF) expression. Although we found that only a proportion of CD4+ CD161++ Vα7.2+ T cells stained for the MR1-tetramer, explaining some of the heterogeneity of CD4+ CD161++ Vα7.2+ T cells, these differences in TF expression were shared with CD4+ CD161++ MR1-tetramer+ cells. These data reveal the functional diversity of human CD161++ Vα7.2+ T cells and indicate potentially distinct roles for the different subsets in vivo