ArticlePLoS pathogens2013
Deletion of IL-4 receptor alpha on dendritic cells renders BALB/c mice hypersusceptible to Leishmania major infection.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 56 citations in OpenAlex.
- Platelet DKK1 promotes tolerogenic dendritic cells and non-healing responses in cutaneous leishmaniasis.iScience · 2026Article
- Article
- A guide to cell-type-specific Cre mouse models in atherosclerosis: from background strains to future directions.Frontiers in cardiovascular medicine · 2026Review
- An overview of host immune responses against Leishmania spp. infections.Human molecular genetics · 2025Review
- The effect of treatment with a non-ionic surfactant vesicular formulation of sodium stibogluconate on host immune responses and serum metabolites in a murine model ofFrontiers in immunology · 2025Article
- IL-4 acts on skin-derived dendritic cells to promote the TThe Journal of allergy and clinical immunology · 2024Article
- Article
- Multimodal control of dendritic cell functions by nociceptors.Science (New York, N.Y.) · 2023Article
- Centrin-deficient Leishmania mexicana confers protection against Old World visceral leishmaniasis.NPJ vaccines · 2022Article
- Cytokines and Signaling Networks Regulating Disease Outcomes in Leishmaniasis.Infection and immunity · 2022Review
- Eosinophils, but Not Type 2 Innate Lymphoid Cells, Are the Predominant Source of Interleukin 4 during the Innate Phase ofPathogens (Basel, Switzerland) · 2022Article
- Immune Responses in Leishmaniasis: An Overview.Tropical medicine and infectious disease · 2022Review
- Centrin-deficient Leishmania mexicana confers protection against New World cutaneous leishmaniasis.NPJ vaccines · 2022Article
- The subunits of IL-12, originating from two distinct cells, can functionally synergize to protect against pathogen dissemination in vivo.Cell reports · 2021Article
- A Cytokine Network Balance Influences the Fate ofFrontiers in immunology · 2021Article
- Interleukin-4 Responsive Dendritic Cells Are Dispensable to Host Resistance AgainstFrontiers in immunology · 2021Article
- Macrophages as host, effector and immunoregulatory cells in leishmaniasis: Impact of tissue micro-environment and metabolism.Cytokine: X · 2020Article
- Unravelling the unsolved paradoxes of cytokine families in host resistance and susceptibility toCytokine: X · 2020Article
- Acute IL-4 Governs Pathogenic T Cell Responses duringImmunoHorizons · 2020Article
- Can We Harness Immune Responses to Improve Drug Treatment in Leishmaniasis?Microorganisms · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In BALB/c mice, susceptibility to infection with the intracellular parasite Leishmania major is driven largely by the development of T helper 2 (Th2) responses and the production of interleukin (IL)-4 and IL-13, which share a common receptor subunit, the IL-4 receptor alpha chain (IL-4Rα). While IL-4 is the main inducer of Th2 responses, paradoxically, it has been shown that exogenously administered IL-4 can promote dendritic cell (DC) IL-12 production and enhance Th1 development if given early during infection. To further investigate the relevance of biological quantities of IL-4 acting on DCs during in vivo infection, DC specific IL-4Rα deficient (CD11c(cre)IL-4Rα(-/lox)) BALB/c mice were generated by gene targeting and site-specific recombination using the cre/loxP system under control of the cd11c locus. DNA, protein, and functional characterization showed abrogated IL-4Rα expression on dendritic cells and alveolar macrophages in CD11c(cre)IL-4Rα(-/lox) mice. Following infection with L. major, CD11c(cre)IL-4Rα(-/lox) mice became hypersusceptible to disease, presenting earlier and increased footpad swelling, necrosis and parasite burdens, upregulated Th2 cytokine responses and increased type 2 antibody production as well as impaired classical activation of macrophages. Hypersusceptibility in CD11c(cre)IL-4Rα(-/lox) mice was accompanied by a striking increase in parasite burdens in peripheral organs such as the spleen, liver, and even the brain. DCs showed increased parasite loads in CD11c(cre)IL-4Rα(-/lox) mice and reduced iNOS production. IL-4Rα-deficient DCs produced reduced IL-12 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and activin A, cytokines previously implicated in promoting Th2 responses. Together, these data demonstrate that abrogation of IL-4Rα signaling on DCs is severely detrimental to the host, leading to rapid disease progression, and increased survival of parasites in infected DCs due to reduced killing effector functions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.