ArticleInfection and immunity2002
In vivo clearance of an intracellular bacterium, Francisella tularensis LVS, is dependent on the p40 subunit of interleukin-12 (IL-12) but not on IL-12 p70.
Article in Infection and immunity, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 126 citations in OpenAlex.
- The immune response toFrontiers in microbiology · 2025Review
- Deletion of Interferon Lambda Receptor Elucidates Susceptibility to the Murine Model of Biliary Atresia.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Article
- IL-12p40 is essential but not sufficient for Francisella tularensis LVS clearance in chronically infected mice.PloS one · 2023Article
- The balance of interleukin-12 and interleukin-23 determines the bias of MAIT1 versus MAIT17 responses during bacterial infection.Immunology and cell biology · 2022Article
- The Sensor Kinase QseC Regulates the Unlinked PmrA Response Regulator and Downstream Gene Expression inJournal of bacteriology · 2020Article
- Review
- Outer Membrane Vesicle Vaccines from Biosafe Surrogates Prevent Acute Lethal Glanders in Mice.Vaccines · 2018Article
- Protective Role for Macrophages in Respiratory Francisella tularensis Infection.Infection and immunity · 2017Article
- Francisella tularensis type B ΔdsbA mutant protects against type A strain and induces strong inflammatory cytokine and Th1-like antibody response in vivo.Pathogens and disease · 2015Article
- Correlates of Vaccine-Induced Protection against Mycobacterium tuberculosis Revealed in Comparative Analyses of Lymphocyte Populations.Clinical and vaccine immunology : CVI · 2015Article
- The transcription factor IRF1 and guanylate-binding proteins target activation of the AIM2 inflammasome by Francisella infection.Nature immunology · 2015Article
- In vivo mechanisms involved in enhanced protection utilizing an Fc receptor-targeted mucosal vaccine platform in a bacterial vaccine and challenge model.Infection and immunity · 2015Article
- IL-23 p19 knockout mice exhibit minimal defects in responses to primary and secondary infection with Francisella tularensis LVS.PloS one · 2014Article
- Host-pathogen interactions and immune evasion strategies in Francisella tularensis pathogenicity.Infection and drug resistance · 2014Review
- IL-10 restrains IL-17 to limit lung pathology characteristics following pulmonary infection with Francisella tularensis live vaccine strain.The American journal of pathology · 2013Article
- Interleukin-17 protects against the Francisella tularensis live vaccine strain but not against a virulent F. tularensis type A strain.Infection and immunity · 2013Article
- Differing effects of interleukin-10 on cutaneous and pulmonary Francisella tularensis live vaccine strain infection.Infection and immunity · 2013Article
- IL-12Rβ2 is critical for survival of primary Francisella tularensis LVS infection.Journal of leukocyte biology · 2013Article
- Interleukin-6 is essential for primary resistance to Francisella tularensis live vaccine strain infection.Infection and immunity · 2013Article
- Subversion of host recognition and defense systems by Francisella spp.Microbiology and molecular biology reviews : MMBR · 2012Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To determine the role of interleukin-12 (IL-12) in primary and secondary immunity to a model intracellular bacterium, we have comprehensively evaluated infection with Francisella tularensis LVS in three murine models of IL-12 deficiency. Mice lacking the p40 protein of IL-12 (p40 knockout [KO] mice) and mice treated in vivo with neutralizing anti-IL-12 antibodies survived large doses of primary and secondary LVS infection but never cleared bacteria and exhibited a chronic infection. In dramatic contrast, mice lacking the p35 protein (p35 KO mice) of heterodimeric IL-12 readily survived large doses of primary sublethal LVS infection as well as maximal secondary lethal challenge, with only a slight delay in clearance of bacteria. LVS-immune wild-type (WT) lymphocytes produced large amounts of gamma interferon (IFN-gamma), but p35 KO and p40 KO lymphocytes produced much less; nonetheless, similar amounts of NO were found in all cultures containing immune lymphocytes, and all immune lymphocytes were equally capable of controlling intracellular growth of LVS in vitro. Purified CD4(+) and CD8(+) T cells from both WT and p40 KO mice controlled intracellular growth, even though T cells from WT mice produced much more IFN-gamma than those from p40 KO mice, and p40 KO T cells did not adopt a Th2 phenotype. Thus, while IL-12 p70 stimulation of IFN-gamma production may be important for bacteriostasis, IL-12 p70 is not necessary for appropriate development of LVS-immune T cells that are capable of controlling intracellular bacterial growth and for clearance of primary or secondary LVS infection. Instead, an additional mechanism dependent on the IL-12 p40 protein, either alone or in another complex such as the newly discovered heterodimer IL-23, appears to be responsible for actual clearance of this intracellular bacterium.
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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.