TGFβ-dependent gene expression profile during maturation of dendritic cells

Fainaru, Ofer; Shay, Tal; Hantisteanu, Shay; Goldenberg, Dalia; Domany, Eytan; Groner, Yoram

doi:10.1038/sj.gene.6364380

Cited by 24 publications

(23 citation statements)

References 30 publications

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“…Others have shown that exposure of DCs to HES products downmodulates their expression of IL-12p40 (31). Similar observations have been made following exposure of DCs to TGF-b (52). In line with a role for TGF-bR signaling in HESmediated inhibition of DC migration, heat inactivation of HES, which destroys the TGF-b-like activity of HES, significantly diminished the inhibitory effect of HES on DC migration.…”

Section: Discussionsupporting

confidence: 70%

Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut

Obieglo

Feng

Bollampalli

et al. 2016

The Journal of Immunology

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Helminth infections have been suggested to impair the development and outcome of Th1 responses to vaccines and intracellular microorganisms. However, there are limited data regarding the ability of intestinal nematodes to modulate Th1 responses at sites distal to the gut. In this study, we have investigated the effect of the intestinal nematode Heligmosomoides polygyrus bakeri on Th1 responses to Mycobacterium bovis bacillus Calmette–Guérin (BCG). We found that H. polygyrus infection localized to the gut can mute BCG-specific CD4+ T cell priming in both the spleen and skin-draining lymph nodes. Furthermore, H. polygyrus infection reduced the magnitude of delayed-type hypersensitivity (DTH) to PPD in the skin. Consequently, H. polygyrus–infected mice challenged with BCG had a higher mycobacterial load in the liver compared with worm-free mice. The excretory–secretory product from H. polygyrus (HES) was found to dampen IFN-γ production by mycobacteria-specific CD4+ T cells. This inhibition was dependent on the TGF-βR signaling activity of HES, suggesting that TGF-β signaling plays a role in the impaired Th1 responses observed coinfection with worms. Similar to results with mycobacteria, H. polygyrus–infected mice displayed an increase in skin parasite load upon secondary infection with Leishmania major as well as a reduction in DTH responses to Leishmania Ag. We show that a nematode confined to the gut can mute T cell responses to mycobacteria and impair control of secondary infections distal to the gut. The ability of intestinal helminths to reduce DTH responses may have clinical implications for the use of skin test–based diagnosis of microbial infections.

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Section: Discussionsupporting

confidence: 70%

Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut

Obieglo

Feng

Bollampalli

et al. 2016

The Journal of Immunology

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“…Furthermore, the spontaneous in situ maturation of TbR1-deficient LCs was associated with downregulation of E-cadherin and increased expression of CCR7, pointing toward an enhanced (e)migratory potential of the cells. Indeed, CCR7 gene activity in DCs can be inhibited by TGF-b signaling in vitro (39), and lower levels of E-cadherin as well as de novo expression of CCR7 are linked to LC dissociation from keratinocytes and migration toward local LNs (15,40).…”

Section: Discussionmentioning

confidence: 99%

TGF-β Is Required To Maintain the Pool of Immature Langerhans Cells in the Epidermis

Kel

Girard-Madoux

Reizis

et al. 2010

The Journal of Immunology

151

142

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“…Among these genes, Tgfb3 and Ifnra2 were up-regulated. The former is involved in inducing TGF-␤ and is considered an inhibitor of DC maturation (10), and the latter is involved in the production of alpha interferon and suppresses IL-12 production (7,32), evidencing for the first time that not only was the encapsulated strain unable to induce activation but that it was capable of activating the gene that regulated the production of alpha interferon and could be involved in the suppression of IL-12 production (7). Thus, the inability of DC to produce IL-12 following stimulation with encapsulated yeast could be related to the induction level of this gene and the activation of other signaling pathways that suppress IL-12.…”

Section: Discussionmentioning

confidence: 99%

The Presence of Capsule inCryptococcus neoformansInfluences the Gene Expression Profile in Dendritic Cells during Interaction with the Fungus

Lupo

Chang²,

Kelsall

et al. 2008

Infect Immun

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The aim of this investigation was to study the effect of polysaccharide capsule on the gene expression in dendritic cells (DC) during their interaction with Cryptococcus neoformans. To this end, we used an encapsulated virulent strain of C. neoformans and a cap59 gene-disrupted acapsular avirulent strain derived from the same genetic background. DC were exposed to encapsulated and acapsular C. neoformans strains for 4 h and 18 h, and their transcriptional profiles were analyzed using the Affymetrix mouse gene chip U74Av2. A large number of DC genes were up-regulated after treatment with the acapsular strain. In particular, we observed the up-regulation of the genes involved in DC maturation, such as cell surface receptors, cytokines, and chemokines (interleukin-12 [IL-12], IL-2, IL-1␣, IL-1␤, IL-6, IL-10, tumor necrosis factor alpha, CCR7, CCL17, CCL22, CCL3, CCL4, CCL7, and CXCL10), membrane proteins, and the genes involved in antigen processing and presentation as well as cell cycle or apoptosis. The chemokine gene expression data were confirmed by real-time reverse transcription-PCR, while the expression of cytokine genes was correlated with their secretion. A completely different pattern of gene expression was observed for DC treated with an encapsulated strain of C. neoformans. In particular, no significant induction was observed in the expression of the genes mentioned above. Moreover, a number of genes, such as those coding for chemokines, were downregulated. These results suggest that the polysaccharide capsule shrouding the cell wall of C. neoformans plays a fundamental role in inducing DC response, highlighting the molecular basis of the true nature of immune silencing exerted by capsular material.Cryptococcus neoformans is an opportunistic encapsulated yeast that causes pulmonary, cerebral, and disseminated infections primarily in patients with defective T-cell immunity, such as those with AIDS, hematological malignancies, and organ transplants (33). The polysaccharide capsule is a major virulence factor of C. neoformans, the concept of which was initially established by studying several acapsular mutants obtained by chemical mutagenesis. These acapsular strains were avirulent in mice, and they were readily ingested by phagocytes, but their ingestion could be inhibited by the addition of purified polysaccharide (3). The effect of the C. neoformans polysaccharide capsule on the host cells can be summarized as follows: it interferes with phagocytosis, blocks the recruitment of inflammatory cells, increases costimulatory molecules, suppresses the delayed-type-hypersensitivity response, and reduces the antibody production in response to fungal infection (11,43).Dendritic cells (DC) are professional antigen-presenting cells that can initiate the innate and adaptive immune response against invading pathogens, thus enabling the decoding of microbe-associated information which then results in qualitatively different adaptive T-helper responses in vitro and in vivo (2, 8).Mouse DC internalize C. neoformans cel...

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TGFβ-dependent gene expression profile during maturation of dendritic cells

Cited by 24 publications

References 30 publications

Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut

Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut

TGF-β Is Required To Maintain the Pool of Immature Langerhans Cells in the Epidermis

The Presence of Capsule inCryptococcus neoformansInfluences the Gene Expression Profile in Dendritic Cells during Interaction with the Fungus

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