scholarly journals Human Macrophages, but Not Dendritic Cells, Are Activated and Produce Alpha/Beta Interferons in Response to Mopeia Virus Infection

2004 ◽  
Vol 78 (19) ◽  
pp. 10516-10524 ◽  
Author(s):  
Delphine Pannetier ◽  
Caroline Faure ◽  
Marie-Claude Georges-Courbot ◽  
Vincent Deubel ◽  
Sylvain Baize
Keyword(s):  
Dendritic Cells ◽  
Adaptive Immune Response ◽  
Hemorrhagic Fever ◽  
Surface Expression ◽  
Lassa Fever ◽  
Lassa Virus ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
The Difference ◽  
Antigen Presenting

ABSTRACT Lassa virus (LV) and Mopeia virus (MV) are closely related members of the Arenavirus genus, sharing 75% amino acid sequence identity. However, LV causes hemorrhagic fever in humans and nonhuman primates, whereas MV cannot induce disease. We have previously shown that antigen-presenting cells (APC)—macrophages (MP) and dendritic cells (DC)—sustain high replication rates of LV but are not activated, suggesting that they play a role in the immunosuppression observed in severe cases of Lassa fever. Here, we infected human APC with MV and analyzed the cellular responses induced. MV infection was productive in MP and even more so in DC. Apoptosis was not induced in either cell type. Moreover, unlike DC, MP were early and strongly activated in response to MV, as shown by the increased surface expression of CD86, CD80, CD54, CD40, and HLA-abc and by the production of mRNA encoding alpha interferon (IFN-α), IFN-β, tumor necrosis factor alpha and interleukin-6. In addition, MV-infected MP produced less of the virus than DC, which was related to the fact that these cells secreted IFN-α. Thus, the strong activation of MP is probably a major event in the control of MV infection and may be involved in the induction of an adaptive immune response in infected hosts. These results may explain the difference in pathogenicity between LV and MV.

scholarly journals Hantavirus Infection of Dendritic Cells

2002 ◽  
Vol 76 (21) ◽  
pp. 10724-10733 ◽  
Author(s):  
Martin J. Raftery ◽  
Annette A. Kraus ◽  
Rainer Ulrich ◽  
Detlev H. Krüger ◽  
Günther Schönrich
Keyword(s):  
Dendritic Cells ◽  
Hemorrhagic Fever ◽  
Hantaan Virus ◽  
Hantavirus Infection ◽  
Necrosis Factor Alpha ◽  
Antigen Uptake ◽  
Antiviral Immune Response ◽  
Factor Alpha ◽  
Antigen Presenting

ABSTRACT Dendritic cells (DCs) play a pivotal role as antigen-presenting cells in the antiviral immune response. Here we show that Hantaan virus (HTNV), which belongs to the Bunyaviridae family (genus Hantavirus) and causes hemorrhagic fever with renal syndrome, productively infects human DCs in vitro. In the course of HTNV infection, DCs did not show any cytopathic effect and viral replication did not induce cell lysis or apoptosis. Furthermore, HTNV did not affect apoptosis-inducing signals that are important for the homeostatic control of mature DCs. In contrast to immunosuppressive viruses, e.g., human cytomegalovirus, HTNV activated immature DCs, resulting in upregulation of major histocompatibility complex (MHC), costimulatory, and adhesion molecules. Intriguingly, strong upregulation of MHC class I molecules and an increased intercellular cell adhesion molecule type 1 expression was also detected on HTNV-infected endothelial cells. In addition, antigen uptake by HTNV-infected DCs was reduced, another characteristic feature of DC maturation. Consistent with these findings, we observed that HTNV-infected DCs stimulated T cells as efficiently as did mature DCs. Finally, infection of DCs with HTNV induced the release of the proinflammatory cytokines tumor necrosis factor alpha and alpha interferon. Taken together, our findings indicate that hantavirus-infected DCs may significantly contribute to hantavirus-associated pathogenesis.

scholarly journals Maturation of Human Dendritic Cells by Cell Wall Skeleton of Mycobacterium bovis Bacillus Calmette-Guérin: Involvement of Toll-Like Receptors

2000 ◽  
Vol 68 (12) ◽  
pp. 6883-6890 ◽  
Author(s):  
Shoutaro Tsuji ◽  
Misako Matsumoto ◽  
Osamu Takeuchi ◽  
Shizuo Akira ◽  
Ichiro Azuma ◽  
...  
Keyword(s):  
Cell Wall ◽  
Dendritic Cells ◽  
Mycobacterium Bovis ◽  
Surface Expression ◽  
Necrosis Factor Alpha ◽  
Mycolic Acids ◽  
Tnf Α ◽  
Toll Like Receptor 2 ◽  
Factor Alpha ◽  
Human Dendritic Cells

ABSTRACT The constituents of mycobacteria are an effective immune adjuvant, as observed with complete Freund's adjuvant. In this study, we demonstrated that the cell wall skeleton of Mycobacterium bovis bacillus Calmette-Guérin (BCG-CWS), a purified noninfectious material consisting of peptidoglycan, arabinogalactan, and mycolic acids, induces maturation of human dendritic cells (DC). Surface expression of CD40, CD80, CD83, and CD86 was increased by BCG-CWS on human immature DC, and the effect was similar to those of interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), heat-killed BCG, and viable BCG. BCG-CWS induced the secretion of TNF-α, IL-6, and IL-12 p40. CD83 expression was increased by a soluble factor secreted from BCG-CWS-treated DC and was completely inhibited by monoclonal antibodies against TNF-α. BCG-CWS-treated DC stimulated extensive allogeneic mixed lymphocyte reactions. The level of TNF-α secreted through BCG-CWS was partially suppressed in murine macrophages with no Toll-like receptor 2 (TLR 2) or TLR4 and was completely lost in TLR2 and TLR4 double-deficient macrophages. These results suggest that the BCG-CWS induces TNF-α secretion from DC via TLR2 and TLR4 and that the secreted TNF-α induces the maturation of DC per se.

scholarly journals Activation of Innate Immune Responses by Haemophilus influenzae Lipooligosaccharide

2014 ◽  
Vol 21 (5) ◽  
pp. 769-776 ◽  
Author(s):  
Joshua Choi ◽  
Andrew D. Cox ◽  
Jianjun Li ◽  
William McCready ◽  
Marina Ulanova
Keyword(s):  
Haemophilus Influenzae ◽  
Surface Expression ◽  
Innate Immune ◽  
Cell Surface Expression ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Hla Dr ◽  
Proinflammatory Activity ◽  
Factor Alpha ◽  
Antigen Presenting

ABSTRACTA Gram-negative pathogenHaemophilus influenzaehas a truncated endotoxin known as lipooligosaccharide (LOS). Recent studies onH. influenzaeLOS highlighted its structural and compositional implications for bacterial virulence; however, the role of LOS in the activation of innate and adaptive immunity is poorly understood. THP-1 monocytes were stimulated with either lipopolysaccharide (LPS) fromEscherichia colior LOS compounds derived fromH. influenzaeEagan, Rd, and Rdlic1 lpsAstrains. Cell surface expression of key antigen-presenting, costimulatory, and adhesion molecules, as well as gene expression of some cytokines and pattern recognition receptors, were studied. Eagan and Rd LOS had a lower capacity to induce the expression of ICAM-1, CD40, CD58, tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) compared to LPS. In contrast, antigen-presenting (HLA-ABC or HLA-DR) and costimulatory (CD86) molecules and NOD2 were similarly upregulated in response to LOS and LPS. LOS from a mutant Rd strain (Rdlic1 lpsA) consistently induced higher expression of innate immune molecules than the wild-type LOS, suggesting the importance of phosphorylcholine and/or oligosaccharide extension in cellular responses to LOS. An LOS compound with a strong ability to upregulate antigen-presenting and costimulatory molecules combined with a low proinflammatory activity may be considered a vaccine candidate to immunize againstH. influenzae.

scholarly journals Lassa Virus Circulation in Small Mammal Populations in Bo District, Sierra Leone

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 28
Author(s):  
Umaru Bangura ◽  
Jacob Buanie ◽  
Joyce Lamin ◽  
Christopher Davis ◽  
Gédéon Ngiala Bongo ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Sierra Leone ◽  
Small Mammal ◽  
Hemorrhagic Fever ◽  
Lassa Fever ◽  
Lassa Virus ◽  
Sierra Leonean ◽  
Bayesian Phylogenetic Analysis ◽  
Prevalent Species ◽  
Lineage Iv

Lassa fever is a viral hemorrhagic fever caused by the Lassa virus LASV, which was first isolated in the rodent Mastomys natalensis in 1974 in Kenema, Sierra Leone. As little is known about the abundance and the presence of LASV in rodents living in the Bo area, we carried out a small mammal longitudinal population survey. A standardized trapping session was performed in various habitats and seasons in six villages over two years (2014–2016) and samples collected were tested for arenavirus IgG and LASV. A Bayesian phylogenetic analysis was performed on sequences identified by PCR. A total of 1490 small mammals were collected, and 16 rodent species were identified, with M. natalensis (355, 24%) found to be the most prevalent species. Forty-one (2.8%) samples were IgG positive, and 31 of these were trapped in homes and 10 in surrounding vegetation. Twenty-nine of 41 seropositive rodents were M. natalensis. We detected four LASV by PCR in two villages, all found in M. natalensis. Phylogenetic analysis showed that the sequences were distributed within the Sierra Leonean clade within lineage IV, distinguishing a Bo sub-clade older than a Kenema sub-clade. Compared to other settings, we found a low abundance of M. natalensis and a low circulation of LASV in rodents in villages around Bo district.

scholarly journals CD4+ CD25+ Foxp3+ Regulatory T Cells, Dendritic Cells, and Circulating Cytokines in Uncomplicated Malaria: Do Different Parasite Species Elicit Similar Host Responses?

2010 ◽  
Vol 78 (11) ◽  
pp. 4763-4772 ◽  
Author(s):  
Raquel M. Gonçalves ◽  
Karina C. Salmazi ◽  
Bianca A. N. Santos ◽  
Melissa S. Bastos ◽  
Sandra C. Rocha ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Parasite Species ◽  
Inflammatory Responses ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Surface Expression ◽  
Interleukin 10 ◽  
Treg Cells ◽  
Experimental Models ◽  
Necrosis Factor Alpha

ABSTRACT Clearing blood-stage malaria parasites without inducing major host pathology requires a finely tuned balance between pro- and anti-inflammatory responses. The interplay between regulatory T (Treg) cells and dendritic cells (DCs) is one of the key determinants of this balance. Although experimental models have revealed various patterns of Treg cell expansion, DC maturation, and cytokine production according to the infecting malaria parasite species, no studies have compared all of these parameters in human infections with Plasmodium falciparum and P. vivax in the same setting of endemicity. Here we show that during uncomplicated acute malaria, both species induced a significant expansion of CD4+ CD25+ Foxp3+ Treg cells expressing the key immunomodulatory molecule CTLA-4 and a significant increase in the proportion of DCs that were plasmacytoid (CD123+), with a decrease in the myeloid/plasmacytoid DC ratio. These changes were proportional to parasite loads but correlated neither with the intensity of clinical symptoms nor with circulating cytokine levels. One-third of P. vivax-infected patients, but no P. falciparum-infected subjects, showed impaired maturation of circulating DCs, with low surface expression of CD86. Although vivax malaria patients overall had a less inflammatory cytokine response, with a higher interleukin-10 (IL-10)/tumor necrosis factor alpha (TNF-α) ratio, this finding did not translate to milder clinical manifestations than those of falciparum malaria patients. We discuss the potential implications of these findings for species-specific pathogenesis and long-lasting protective immunity to malaria.

scholarly journals Tumour necrosis factor-alpha but not lipopolysaccharide enhances preference of murine dendritic cells for Th2 differentiation

Immunology ◽  
2003 ◽  
Vol 108 (1) ◽  
pp. 42-49 ◽  
Author(s):  
Kazuhiro Kikuchi ◽  
Yoshiki Yanagawa ◽  
Toshimasa Aranami ◽  
Chikako Iwabuchi ◽  
Kazuya Iwabuchi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Th2 Differentiation ◽  
Necrosis Factor

Interferon-Gamma and Tumor Necrosis Factor-Alpha Promote the Binding of Dendritic Cells to Fibronectin

Pathobiology ◽  
1994 ◽  
Vol 62 (3) ◽  
pp. 120-126 ◽  
Author(s):  
Thomas Chang-Yao Tsao ◽  
Weijia Xia ◽  
Gary M. Rodberg ◽  
Clare E. Pinto ◽  
Richard L. Kradin
Keyword(s):  
Dendritic Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Interferon Gamma ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

scholarly journals Differential Immune Responses to Hemorrhagic Fever-Causing Arenaviruses

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 138 ◽  
Author(s):  
Mantlo ◽  
Paessler ◽  
Huang
Keyword(s):  
Clinical Importance ◽  
Hemorrhagic Fever ◽  
Lassa Fever ◽  
Innate Immune ◽  
Host Immune System ◽  
Lassa Virus ◽  
Type I ◽  
Highly Pathogenic ◽  
The Family ◽  
Pro Inflammatory Cytokines

The family Arenaviridae contains several pathogens of major clinical importance. The Old World (OW) arenavirus Lassa virus is endemic in West Africa and is estimated to cause up to 300,000 infections each year. The New World (NW) arenaviruses Junín and Machupo periodically cause hemorrhagic fever outbreaks in South America. While these arenaviruses are highly pathogenic in humans, recent evidence indicates that pathogenic OW and NW arenaviruses interact with the host immune system differently, which may have differential impacts on viral pathogenesis. Severe Lassa fever cases are characterized by profound immunosuppression. In contrast, pathogenic NW arenavirus infections are accompanied by elevated levels of Type I interferon and pro-inflammatory cytokines. This review aims to summarize recent findings about interactions of these pathogenic arenaviruses with the innate immune machinery and the subsequent effects on adaptive immunity, which may inform the development of vaccines and therapeutics against arenavirus infections.

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