Th2 responses are primed by skin dendritic cells with distinct transcriptional profiles

Connor, Lisa M.; Tang, Shiau-Choot; Cognard, Emmanuelle; Ochiai, Sotaro; Hilligan, Kerry L.; Old, Samuel I; Pellefigues, Christophe; White, Ruby; Patel, Deepa; Smith, Alexander; Eccles, David; Lamiable, Olivier; McConnell, Melanie J.; Ronchese, Franca

doi:10.1084/jem.20160470

Cited by 72 publications

(123 citation statements)

References 72 publications

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“…DCs from skin LN exposed to Nippostrongylus brasiliensis showed transcriptional changes of different DC subsets (Connor et al, 2017). Generally, DCs are pivotal in eliciting Th2 cell responses in vivo .…”

Section: Discussionmentioning

confidence: 99%

Toxoplasma Co-infection Prevents Th2 Differentiation and Leads to a Helminth-Specific Th1 Response

Ahmed

French

Kühl³

et al. 2017

Front. Cell. Infect. Microbiol.

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Nematode infections, in particular gastrointestinal nematodes, are widespread and co-infections with other parasites and pathogens are frequently encountered in humans and animals. To decipher the immunological effects of a widespread protozoan infection on the anti-helminth immune response we studied a co-infection with the enteric nematode Heligmosomoides polygyrus in mice previously infected with Toxoplasma gondii. Protective immune responses against nematodes are dependent on parasite-specific Th2 responses associated with IL-4, IL-5, IL-13, IgE, and IgG1 antibodies. In contrast, Toxoplasma gondii infection elicits a strong and protective Th1 immune response characterized by IFN-γ, IL-12, and IgG2a antibodies. Co-infected animals displayed significantly higher worm fecundity although worm burden remained unchanged. In line with this, the Th2 response to H. polygyrus in co-infected animals showed a profound reduction of IL-4, IL-5, IL-13, and GATA-3 expressing T cells. Co-infection also resulted in the lack of eosinophilia and reduced expression of the Th2 effector molecule RELM-β in intestinal tissue. In contrast, the Th1 response to the protozoan parasite was not diminished and parasitemia of T. gondii was unaffected by concurrent helminth infection. Importantly, H. polygyrus specific restimulation of splenocytes revealed H. polygyrus-reactive CD4+ T cells that produce a significant amount of IFN-γ in co-infected animals. This was not observed in animals infected with the nematode alone. Increased levels of H. polygyrus-specific IgG2a antibodies in co-infected mice mirrored this finding. This study suggests that polarization rather than priming of naive CD4+ T cells is disturbed in mice previously infected with T. gondii. In conclusion, a previous T. gondii infection limits a helminth-specific Th2 immune response while promoting a shift toward a Th1-type immune response.

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Section: Discussionmentioning

confidence: 99%

Toxoplasma Co-infection Prevents Th2 Differentiation and Leads to a Helminth-Specific Th1 Response

Ahmed

French

Kühl³

et al. 2017

Front. Cell. Infect. Microbiol.

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“…Moreover, the nature of the initial stimulus is also likely to have an impact on the resulting response. 127 For instance, dendritic cells in the skin of mice that are exposed to N. brasiliensis larvae or the contact sensitizer dibutyl phthalate (both of which induce type 2 immunity) acquire distinct transcriptional profiles, revealing a previously unappreciated role for type I interferons during parasite infection, 128 and highlighting the complicated nature of pathogen recognition by the innate immune system. Interestingly, some studies suggest that ILC, 129-131 basophils, [132][133][134] and eosinophils 135,136 can express major histocompatibility complex class II and directly prime Th2 responses, notably upon N. brasiliensis 131 and T. muris 132 infections, with each cell type having been shown to migrate to the mesenteric lymph nodes during infection.…”

Section: Inductionmentioning

confidence: 99%

Immunity to gastrointestinal nematode infections

2018

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“…The expressions of both chaperones of HSP90, namely endoplasmin (HSP90B1) and HSP90AA1, were increased with SEA stimulation. Interestingly, HSP90 is a protein that is important for type I interferon production [29] , which was recently found to be a key transcriptional signature of murine skin DCs and that enable them to drive Th2 responses in response to helminth antigens [30] . However, given that HSP90AA1 was also observed to be upregu- A heat map of regulated proteins of differently stimulated monocyte-derived (mo)DCs.…”

Section: Effects Of Polarizing Stimuli On the Human DC Proteomementioning

confidence: 99%

Human Dendritic Cells with Th2-Polarizing Capacity: Analysis Using Label-Free Quantitative Proteomics

Hussaarts

Kaisar²,

Güler³

et al. 2017

Int Arch Allergy Immunol

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Background: Dendritic cells (DCs) are the sentinels of the immune system. Upon recognition of a pathogen, they mature and migrate to draining lymph nodes to prime and polarize T cell responses. Although it is known that helminths and helminth-derived molecules condition DCs to polarize T helper (Th) cells towards Th2, the underlying mechanisms remain incompletely understood. Objectives: The aim of this study was to conduct a proteome analysis of helminth antigen-stimulated DCs in order to gain more insight into the cellular processes associated with their ability to polarize immune responses. Methods: We analyzed the maturation and polarization of monocyte-derived DCs from 9 donors at 2 different time points after stimulation with different Th1- and Th2-polarizing pathogen-derived molecules. The samples were measured using liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry for relative quantitation. Results: Lipopolysaccharide-induced maturation promoted the expression of proteins related to metabolic, cellular, and immune system processes. Th1-polarizing DCs, conditioned by IFN-γ during maturation, displayed accelerated maturation by differentially expressing cytoskeletal proteins and proteins involved in immune regulation. The stimulation of DCs with soluble egg antigens and omega-1 derived from Schistosoma mansoni, which are both Th2-inducing stimuli, increased 60S acidic ribosomal protein P2, and vesicle amine transferase 1 while decreasing the expression of proteins related to antigen processing and presentation. Conclusion: Our data indicate that not only proteins involved in the interaction between T cells and DCs at the level of the immunological synapse, but also those related to cellular metabolism and stress, may promote Th2 polarization.

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Th2 responses are primed by skin dendritic cells with distinct transcriptional profiles

Abstract: Connor et al. show that transcriptomic profiling of DCs exposed to two different Th2 stimuli in vivo reveals large numbers of differentially expressed genes but few similarities between conditions.

Cited by 72 publications

References 72 publications

Toxoplasma Co-infection Prevents Th2 Differentiation and Leads to a Helminth-Specific Th1 Response

Toxoplasma Co-infection Prevents Th2 Differentiation and Leads to a Helminth-Specific Th1 Response

Immunity to gastrointestinal nematode infections

Human Dendritic Cells with Th2-Polarizing Capacity: Analysis Using Label-Free Quantitative Proteomics

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