Human Neonatal Dendritic Cells Are Competent in MHC Class I Antigen Processing and Presentation

Neonates are clearly more susceptible to severe disease following infection with a variety of pathogens than are adults. However, the causes for this are unclear and are often attributed to immunological immaturity. While several aspects of immunity differ between adults and neonates, the capacity of dendritic cells in neonates to process and present antigen to CD8+ T cells remains to be addressed. We used human CD8+ T cell clones to compare the ability of neonatal and adult monocyte-derived dendritic cells to present or process and present antigen using the MHC class I pathway. Specifically, we assessed the ability of dendritic cells to present antigenic peptide, present an HLA-E–restricted antigen, process and present an MHC class I-restricted antigen through the classical MHC class I pathway, and cross present cell-associated antigen via MHC class I. We found no defect in neonatal dendritic cells to perform any of these processing and presentation functions and conclude that the MHC class I antigen processing and presentation pathway is functional in neonatal dendritic cells and hence may not account for the diminished control of pathogens

BCG vaccination: a role for vitamin D?

BCG vaccination is administered in infancy in most countries with the aim of providing protection against tuberculosis. There is increasing interest in the role of vitamin D in immunity to tuberculosis. This study objective was to determine if there was an association between circulating 25(OH)D concentrations and BCG vaccination status and cytokine responses following BCG vaccination in infants

Apoptosis as pathogenic mechanism of infection with vesicular stomatitis virus. Evidence in primary bovine fibroblast cultures.

To determine whether fibroblasts from Blanco Orejinegro cattle, exhibit any level of resistance to infection against vesicular stomatitis virus (VSV) serotypes Indiana (VSV-I) or New Jersey (VSV-NJ), 30 fibroblast cultures were phenotyped to evaluate their resistance/susceptibility. Thirty three % of Blanco Orejinegro fibroblast cultures were classified as very resistant, 50% as resistant, and 17% as susceptible to VSV-I infection, whereas 20% were classified as very resistant, 50% as resistant and 30% as susceptible to VSV-NJ infection. Therefore, there appears to be a large variation in phenotypic polymorphism among the fibroblasts to infection by VSV. To elucidate the mechanisms responsible for this diversity, we searched for a possible relationship between resistance/susceptibility and production of factors with antiviral activity; however fibroblasts did not secrete factors with antiviral activity. We examined also whether apoptosis where induced by infection and its correlation with the polymorphism of resistance/susceptibility to VSV. Using morphological analyses, hypoploidy measurements, and level of phosphatidyl serine expression, high levels of apoptosis were measured in VSV infected fibroblasts. However, no correlation exists between apoptosis and the category of resistance/susceptibility to infection, indicating that apoptosis is a pathogenic mechanism of VSV.0000-0002-1447-14580000-0002-7351-8738julian.ruizs@[email protected]

Maturation of CD4(+) Regulatory T Lymphocytes and of Cytokine Secretions in Infants Born Prematurely.

To characterize the maturation of CD4(+) regulatory T lymphocytes (Treg) and of cytokine productions in preterm infants during their first 16 months of life.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Differential Expression of Toll-like Receptors in Dendritic Cells of Patients with Dengue during Early and Late Acute Phases of the Disease

<p>Background: Dengue hemorrhagic fever (DHF) is observed in individuals that have pre-existing heterotypic dengue antibodies and is associated with increased viral load and high levels of pro-inflammatory cytokines early in infection. Interestingly, a recent study showed that dengue virus infection in the presence of antibodies resulted in poor stimulation of Toll-like receptors (TLRs), thereby facilitating virus particle production, and also suggesting that TLRs may contribute to disease pathogenesis.</p><p>Methodology/Principal Findings: We evaluated the expression levels of TLR2, 3, 4 and 9 and the co-stimulatory molecules CD80 and CD86 by flow cytometry. This was evaluated in monocytes, in myeloid and plasmacytoid dendritic cells (mDCs and pDCs) from 30 dengue patients with different clinical outcomes and in 20 healthy controls. Increased expression of TLR3 and TLR9 in DCs of patients with dengue fever (DF) early in infection was detected. In DCs from patients with severe manifestations, poor stimulation of TLR3 and TLR9 was observed. In addition, we found a lower expression of TLR2 in patients with DF compared to DHF. Expression levels of TLR4 were not affected. Furthermore, the expression of CD80 and CD86 was altered in mDCs and CD86 in pDCs of severe dengue cases. We show that interferon alpha production decreased in the presence of dengue virus after stimulation of PBMCs with the TLR9 agonist (CpG A). This suggests that the virus can affect the interferon response through this signaling pathway.</p><p>Conclusions/Significance: These results show that during dengue disease progression, the expression profile of TLRs changes depending on the severity of the disease. Changes in TLRs expression could play a central role in DC activation, thereby influencing the innate immune response.</p>

Activation of cord blood myeloid dendritic cells by Trypanosoma cruzi and parasite-specific antibodies, proliferation of CD8+ T cells, and production of IFN-γ.

We previously reported that Trypanosoma cruzi, the agent of Chagas disease, induces in congenitally infected fetuses a strong, adult-like parasite-specific CD8(+) T cell response producing IFN-γ (Hermann et al. in Blood 100:2153-2158, 2002). This suggests that the parasite is able to overcome the immaturity of neonatal antigen presenting cells, an issue which has not been previously addressed. We therefore investigated in vitro the ability of T. cruzi to activate cord blood DCs and compared its effect to that on adult cells. We show that T. cruzi induces phenotypic maturation of cord blood CD11c(+) myeloid DCs (mDCs), by enhancing surface expression of CD40, CD80, and CD83, and that parasite-specific IgG purified from cord blood of neonates born to T. cruzi-infected mothers amplify such expression. CD83, considered as the best marker of mature DCs, reaches higher level on cord blood than on adult mDCs. Allo-stimulation experiments showed that T. cruzi-activated cord blood mononuclear cells enriched in DCs (eDCs) stimulate proliferation of cord blood and adult CD3(+) T cells to a similar extent. Of note, T. cruzi-activated eDCs from cord blood trigger more potent proliferation of CD8(+) than CD8(-) (mainly CD4(+)) adult T cells, a feature not observed with adult eDCs. T cell proliferation is associated with IFN-γ release and down-regulation of IL-13 production. These data show that T. cruzi potently activates human cord blood mDCs and endows eDCs to trigger CD8(+) T cell proliferation and favor type 1 immune response. Interestingly, maternal antibodies can strengthen the development of mature DCs that might contribute to overcome the immunological immaturity associated with early life.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Immune Approaches for the Prevention of Breast Milk Transmission of HIV-1

Mother-to-child transmission (MTCT) of HIV-1 infection remains a significant cause of new HIV-1 infections, despite the increasing implementation of prevention strategies using antiretroviral therapy (ART) and the resulting decline in infections across the developing world. In 2009, the UNAIDS global report estimated 370,000 children under the age of 15 years were newly infected with HIV-1 (refer UNAIDS Report on the global AIDS epidemic, 2010 http://www.unaids.org/globalreport/Global-report.htm), most of whom acquired the infection from their mothers in low- and middle-income countries. Even with substantial progress, challenges remain for poor countries in providing comprehensive screening programs for pregnant women and implementing the full range of prevention services for those identified as HIV-1-infected. Although antiretroviral regimens and risk reduction counseling have been successfully used for pregnant women and their infants in many parts of the developing world, full implementation of these programs remains a challenge in many countries, especially where antenatal clinical attendance and HIV-1 screening is not yet widespread. In addition, potential toxicities of and development of drug resistance to ART in both mother and child are concerns. Therefore, the development of a safe effective immunoprophylaxis regimen begun at birth and continuing during breastfeeding, perhaps alongside neonatal chemoprophylaxis, remains an area of active research interest. An ideal pediatric vaccine for prevention of MTCT (PMTCT) would combine the immediacy of passive immunization designed to protect the infant during the first vulnerable weeks of life with the durability of active immunization to protect against the repeated low-dose homologous virus exposure delivered multiple times a day via breastfeeding. © 2012 Springer Science+Business Media New York