Effect of intrauterine HIV-1 exposure on the frequency and function of uninfected newborns’ dendritic cells

Velilla, Paula A.; Montoya, Carlos; Hoyos, Álvaro Turriago; Moreno, María Eugenia; Chougnet, Claire; Rugeles, Marı́a Teresa

doi:10.1016/j.clim.2007.11.004

Cited by 46 publications

(47 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

Section: Discussionsupporting

confidence: 71%

“…The level of B7-H1 expression induced by maturation was significantly stronger in mDC as compared to pDC. This finding is partially supported by in vivo data obtained with cancer and infectious disease models, where mDC have been shown to be the preferential target cell for B7-H1 induction [7,25,[38][39][40].The repertoire of TLR ligands, providing direct stimulation of B7-H1 in mDC (poly I:C stimulates TLR3, LPS stimulates TLR4) and pDC (CpG stimulates TLR9), correlates with the previously published expression of the respective TLR in human DC subsets (summarized in [41]), suggesting a direct correlation of TLR activation and B7-H1 upregulation. In aggregate, our data show that in nonpathological steady-state conditions human blood circulating mDC and pDC posses a rather immature phenotype and low B7-H1 expression, while upon engagement of defined TLR, the expression of B7-H1 is upregulated and accompanied by expression of classical T-cell costimulatory molecules.…”

supporting

confidence: 71%

See 1 more Smart Citation

ERK/p38 MAP‐kinases and PI3K are involved in the differential regulation of B7‐H1 expression in DC subsets

Karakhanova¹,

Meisel²,

Ring³

et al. 2009

Eur J Immunol

View full text Add to dashboard Cite

Regulatory molecules of the B7-H-family expressed by DC are important for immune homeostasis, but their regulation is largely unknown. When investigating the pathways regulating B7-H1 expression in monocyte-derived DC (MoDC), freshly isolated myeloid DC (mDC) and plasmacytoid DC, respectively, we showed that in MoDC and mDC B7-H1 expression was upregulated by a standard cytokine cocktail, poly I:C or LPS. MoDC utilize ERK and PI3K pathways to upregulate B7-H1 in response to cytokines, whereas p38 kinase was predominantly utilized in response to poly I:C. In mDC, ERK and p38 pathways are involved in B7-H1 regulation, and similar to MoDC, mainly p38 signaling was required for poly I:C-induced expression of B7-H1. Plasmacytoid DC responded only to CpG with upregulation of B7-H1 and in addition to p38 also utilized the PI3K and ERK pathways to regulate B7-H1 expression. As a functional consequence of B7-H1 expression on DC, we demonstrate downmodulation of IFN-c production in T cells. Thus, the differential regulation of B7-H1 on DC subsets may suppress immune responses variably, depending on the target DC population. Further analysis of the regulatory mechanisms may facilitate the development of new immunosuppressive therapies, utilizing the regulation of B7-H1 expression on DC.Key words: B7-H1 regulatory molecules . Dendritic cells . Signal transduction Supporting Information available online IntroductionMechanisms that limit undesirable T-cell activation are important for the maintenance of peripheral tolerance. In particular, the expression of positive or negative regulatory molecules on APC is crucial. In humans, the most potent type of APC are DC, which consist of myeloid and plasmacytoid subpopulations as well as Langerhans cells. Although originally defined by their potent T-cell activation capacity, DC are obviously also involved in the maintenance of peripheral tolerance and immune homeostasis, as several types of tolerogenic DC have been described [1,2].To provide signals for the induction of T-cell immunity, DC must be matured and activated with microbial agents or cytokines, among others, in order to become equipped with an appropriate set of costimulatory molecules [3]. In contrast, immature DC lack cytokine production and surface expression of several T-cell costimulatory molecules and, Ã These authors contributed equally to this work. hence, have been shown to tolerize T cells or to induce regulatory T cells [4,5].In addition, DC can also express T-cell regulatory molecules that limit immune responses and protect the body from overwhelming injury. One recently identified molecule, B7-H1 (CD274, PD-L1-programmed death receptor ligand 1), has been implicated in the downregulation of immune responses in different human diseases, such as hepatitis, chronic gastritis, renal inflammatory disease, autoimmunity and different types of cancer [6][7][8][9][10][11][12].B7-H1 is a type 1 transmembrane glycoprotein and a member of the B7 superfamily and one of two ligands for the CD28 homologue programmed death-1...

show abstract

Section: Discussionsupporting

confidence: 71%

supporting

confidence: 71%

ERK/p38 MAP‐kinases and PI3K are involved in the differential regulation of B7‐H1 expression in DC subsets

Karakhanova¹,

Meisel²,

Ring³

et al. 2009

Eur J Immunol

View full text Add to dashboard Cite

show abstract

“…7 This elevated mortality as well as the observed increased risks of hospitalization in our study may be the result of immunologic deficits that have been documented in HEU infants. [41][42][43][44] The degree of maternal immunosuppression has been shown to be an important predictor of infant survival, and ART use in pregnancy may have an impact on infant birth weight and immune response, but we did not have data on maternal CD4+ T-cell count or use of ART during pregnancy in our study to assess this association. 45,46 Other possible reasons for the increased risk of severe outcomes observed in HEU infants include possible increased exposure to maternally derived pathogens including cytomegalovirus, reduced transfer of protective antibodies from severely immunosuppressed mothers, and possible impaired responses to some vaccines.…”

Section: Discussionmentioning

confidence: 97%

Epidemiology of Acute Lower Respiratory Tract Infection in HIV-Exposed Uninfected Infants

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The HEU infants also presented the enhanced expression of CD40L on activated T lymphocytes (27), higher B-lymphocyte apoptosis levels (20), and alterations in dendritic cells (36) that may interfere with the antigen presentation and immune response to T-dependent antigens.…”

Section: Discussionmentioning

confidence: 99%

Impaired Humoral Response to Vaccines among HIV-Exposed Uninfected Infants

Abramczuk

Mazzola

Moreno

et al. 2011

Clin. Vaccine Immunol.

View full text Add to dashboard Cite

Little is known about the vaccine protective response for infants born from HIV-infected mothers. We evaluated the antibody response to hepatitis B, tetanus, and diphtheria vaccine in vertically HIV-exposed uninfected infants and compared them to those of control infants not exposed to the virus. The quantitative determination of specific neutralizing antibodies against hepatitis B, diphtheria, and tetanus were performed blindly on serum samples. The results showed that 6.7% of the HIV-exposed uninfected individuals were nonresponders to hepatitis B vaccine (anti-HBs titer, <10 mIU/ml), and 64.4% were very good responders (anti-HBs titer, >1,000 mIU/ml), whereas only 3.6% of the nonexposed infants were nonresponders ( 2 ‫؍‬ 10.93; 1 df). The HIV-exposed uninfected infants showed protective titers for diphtheria and tetanus but lower geometric mean anti-tetanus titers compared to those of the HIV-unexposed infants. Our data point to the necessity of evaluating vaccine immune responses in these children and reinforced that alterations in lymphocyte numbers and functions reported for newborns from HIV-infected mothers interfere with the vaccine response.

show abstract

Effect of intrauterine HIV-1 exposure on the frequency and function of uninfected newborns’ dendritic cells

Cited by 46 publications

References 50 publications

ERK/p38 MAP‐kinases and PI3K are involved in the differential regulation of B7‐H1 expression in DC subsets

ERK/p38 MAP‐kinases and PI3K are involved in the differential regulation of B7‐H1 expression in DC subsets

Epidemiology of Acute Lower Respiratory Tract Infection in HIV-Exposed Uninfected Infants

Impaired Humoral Response to Vaccines among HIV-Exposed Uninfected Infants

Contact Info

Product

Resources

About